Vision changes are a big part of the side effects of both standard treatment and several of the additional drugs either approved (boceprevir, telaprevir) or under study for treating Hepatitis C (RO5024048 RG7128). They can include blurry vision, changes in the strength of your vision, sparkles or light shows within or at the edge of your visual field and worst of all macular degeneration. The effects can vary in intensity during the course of treatment. Most of the visual side effects reverse after treatment is ended save for macular degeneration, which is permanent. In my case, the effects seem to be slowly reversing themselves.
In this post (about 6 paragraphs down) there is a description of the onset of the visual side effects when treatment began. At the time the primary effect seemed to be a reduction in my ability to focus on things that were close-up in my visual field. I lost most of my natural monocular vision in which the left eye focused up close the right eye focused at a distance. It eventually progressed to the point that, at the end of treatment, there was little difference between the two eyes. The left still focused a touch better close up and the right a touch better at a distance, but there was no longer a significant difference.
There was also some variation in the strength of vision. It seemed that from month to month there were variations in the amount of short sightedness I was victim to. Sometimes, it seemed my glasses were not nearly strong enough and other times they were far too strong. I took to not wearing them most of the time and carrying around reading glasses for when there was a need to focus closely (for those of you in the San Francisco Bay Area, Ichiban Kan the Japanese discount store has reading glasses for $1.50 per pair; and stylin ones at that). I decided not to get new glasses or even try to determine my prescription until the treatment was over.
Several months after I had been dropped from the experimental study and was on the standard treatment, I began to notice that there were sparkles in my visual field. They were not large nor were they particularly intrusive, but they were apparent when I wasn’t focusing on a specific area. They were also apparent at the edges of the visual field, particularly in low light. I kept thinking that I saw something out of the corner of my eye and when I tried to turn and focus on it, there was never anything there. It took a while to realize that it was due to the sparklies and not to flies, birds, mice, rain, ghosts or any of the other things that appear in the corners of your vision.
Now that 9 weeks have passed since finishing the interferon and Ribavirin treatment, there has been some reversal of the visual side effects. The sparklies in the visual field and at the corners of my eyes are mostly gone. They still appear when I am very tired, but they may have always done that and I wouldn’t know it given the state of my memory. The variations in my strength of vision have stabilized as well. There are no longer times when I cannot wear glasses because they make my eyes hurt. Perhaps it is time to visit the eye doctor and get a new prescription and even new glasses (Costco here we come). There has been no change in the loss of monocular vision. My two eyes remain slightly different, but the old ability to read with the left eye and focus long-distance with the right seems to be gone permanently.
The side effect of the eyes getting tired rapidly during reading and watching a movie, TV or computer screen has also begun to reverse. So much so that this past weekend my lovely wife and I were able to take in two movies in two days. These were not “films” either with long static takes of characters talking or meditative pans across beautiful scenery. These were eye-taxing action films with rapid changes in focus, explosions, chase scenes and all the things you watch movies on the big screen for. Yes, we saw “Cowboys and Aliens” and “Rise of the Planet of the Apes” - two brilliant examples of all that is right in Hollywood filmmaking. At least with Hep C, the treatment doesn’t make apes smarter and people dead. We got that going for us…
Showing posts with label RO5024048. Show all posts
Showing posts with label RO5024048. Show all posts
Tuesday, September 6, 2011
Tuesday, August 16, 2011
Changes In Visualizations During Treatment
There is a great deal of evidence that creative visualization can influence the actual physical and mental performance of people in the real world. Studies have been done on academic test performance and athletic performance to use two examples and the evidence has indicated that if one group spends a specific amount of time visualizing successfully completing a task and another group spends the same amount of time practicing the task, the two groups have similar results upon undertaking the task. There is also evidence that the same sort of creative visualization influences recovery rates and treatment outcomes in disease situations.
It was with that in mind that I created my own visualization when I started HEP C treatment in the RG7128, RO5024048 clinical trial. I imagined that the polymerase inhibitor RG7128 was an armored division of fast moving powerful tanks that struck quickly and with lethal force at the HEP C virus. The interferon and Ribavirin were the methodical infantry units that followed the tanks and mopped up the remaining resistance from viruses that were either entrenched or bypassed by the fast moving armor. I visualized that image often throughout the clinical trial. After being tossed out of the clinical trial because of a viral breakthrough, my visualization metaphor changed. My tanks had run out of gas and were now abandoned by the side of the road.
After transitioning into Standard of Care therapy I still used a military image when I thought about my battle with the HEP C virus, but now it had switched to an image of slogging trench warfare with my infantry (interferon and Ribavirin) in hand-to-hand combat with the virus. It was going to be a 12 month struggle but they were attacking an already weakened foe and had strength of numbers and better supplies on their side. I used this image for several months and sure enough, after 14 weeks the numbers came back negative indicating my infantry were winning.
Then there was the possible viral breakthrough in December after six months of treatment and the subsequent return to being virally negative in January. The metaphor was fairly tattered by then but I tried to hold to it. As the months of treatment ground on and I eventually went on disability, the only military image that seemed to fit was the battle of Stalingrad; except I didn’t know which side I was on. Holding on till the end of treatment was the only concern. This carries on the military metaphor quite well actually. At the end of a long tour of duty on the front lines, the primary concern a soldier has is surviving until it is over.
At the end of treatment, the viral load was undetectable and the viral activity was negative so we can assume that the visualization was either successful and contributed to the treatment or at least did not inhibit the effectiveness of the treatment. I would recommend the technique to anyone undergoing any kind of treatment for disease. There is no need to use a military image, whatever is vivid and emotionally engaging will work. It is no doubt easier to maintain the metaphor for shorter treatments than longer ones, but anything that can help healing is worth pursuing. Just hope your metaphor doesn’t run out of gas on the side of the road. There is nothing sadder imaginarily speaking than watching your elite troops quit the battlefield.
It was with that in mind that I created my own visualization when I started HEP C treatment in the RG7128, RO5024048 clinical trial. I imagined that the polymerase inhibitor RG7128 was an armored division of fast moving powerful tanks that struck quickly and with lethal force at the HEP C virus. The interferon and Ribavirin were the methodical infantry units that followed the tanks and mopped up the remaining resistance from viruses that were either entrenched or bypassed by the fast moving armor. I visualized that image often throughout the clinical trial. After being tossed out of the clinical trial because of a viral breakthrough, my visualization metaphor changed. My tanks had run out of gas and were now abandoned by the side of the road.
After transitioning into Standard of Care therapy I still used a military image when I thought about my battle with the HEP C virus, but now it had switched to an image of slogging trench warfare with my infantry (interferon and Ribavirin) in hand-to-hand combat with the virus. It was going to be a 12 month struggle but they were attacking an already weakened foe and had strength of numbers and better supplies on their side. I used this image for several months and sure enough, after 14 weeks the numbers came back negative indicating my infantry were winning.
Then there was the possible viral breakthrough in December after six months of treatment and the subsequent return to being virally negative in January. The metaphor was fairly tattered by then but I tried to hold to it. As the months of treatment ground on and I eventually went on disability, the only military image that seemed to fit was the battle of Stalingrad; except I didn’t know which side I was on. Holding on till the end of treatment was the only concern. This carries on the military metaphor quite well actually. At the end of a long tour of duty on the front lines, the primary concern a soldier has is surviving until it is over.
At the end of treatment, the viral load was undetectable and the viral activity was negative so we can assume that the visualization was either successful and contributed to the treatment or at least did not inhibit the effectiveness of the treatment. I would recommend the technique to anyone undergoing any kind of treatment for disease. There is no need to use a military image, whatever is vivid and emotionally engaging will work. It is no doubt easier to maintain the metaphor for shorter treatments than longer ones, but anything that can help healing is worth pursuing. Just hope your metaphor doesn’t run out of gas on the side of the road. There is nothing sadder imaginarily speaking than watching your elite troops quit the battlefield.
Tuesday, December 21, 2010
The Magic Bullet Theory
Waiting for the “Next Best Thing”
Last Tuesday was the annual Holiday Pot Luck for the twice-monthly Hepatitis C support group that meets in the California Pacific Medical Center Pathology Conference room. There were about two dozen people there and, in the tradition of potluck dinners everywhere, enough food for twice that number. Best of all, there were plenty of desserts.
Of the two dozen people or so people attending, about half were either currently in treatment or had successfully completed treatment; another quarter had undergone treatment and either failed to respond or the virus had reappeared after the completion of treatment and the last quarter had yet to make a decision about treatment. About half the folks who had successfully completed treatment and never had a recurrence of the virus were people with Hepatitis C genotype 2. This genotype has about an 80% chance of clearance, and excellent prospects of a sustained viral response, with 24 weeks of standard interferon and ribavirin treatment.
After people had settled down with their plates of food and glasses of non-alcoholic libations (ginger potions of all sorts were quite popular), everyone reported on their general state of health, how they felt and any significant issues they had that might be caused or intensified by the disease or their treatment status. Several common themes emerged as people told their stories.
The people who had successfully completed treatment reported that by and large they felt they were back to normal functioning (one individual reported that she felt that after 2 years she still did not feel she was back to her previous cognitive function level). They felt their energy had returned, they no longer had shortness of breath, their strength was back and generally they were physically in good condition. Most felt that their mental faculties and their memory had returned to pre-treatment levels as well. To a person, they reported that it took considerably longer to return to full function than the time that is considered standard by the medical establishment. The usually quoted time to recover from the effects of interferon, ribavirin and the other associated drugs used in treatment is 3 to 6 months. Everyone reported that the time it took them to recover from treatment was in the range of 6 months to 1 year with a few reporting longer times than that.
The people currently in treatment (and for that matter, the folks who had completed treatment) reported two side effects as most debilitating: fatigue and brain fog. The fatigue ranged from merely difficult to extreme with no one reporting only mild fatigue. That said, person after person stated that the most irritating and frustrating side effect was the cognitive deficit associated with interferon brain fog. It was not just the increased memory difficulties, it was the inability to concentrate, the ease of distraction, the loss of train of thought that drove everyone crazy. Most folks also reported nausea of varying degrees, insomnia, sweats etc.; but those paled in comparison to the frustration of brain fog and the annoyance of being tired all the time.
The rest of the people at the meeting, the non-responders to treatment and the people yet to attempt treatment, all had the same outlook: they were waiting for the new and better drugs to become available. They had very different reasons for this viewpoint, but it was surprising to see the uniformity of their point of view.
The non-responders and fail-to-sustainers had all failed at the standard interferon and ribavirin treatment. They and their doctors had come to the conclusion that the two drug standard treatment was not going to successfully defeat the virus in their bodies. They need the additional punch of one of the new drugs in order to have a real chance at success. You can’t argue with that conclusion, when what is available has failed, you have to await further developments to move forward.
The people who had not done any treatment had different reasons for waiting for the next new and better drugs. Many were afraid of the side effects but most were looking for a therapy with a better chance of success that the standard therapy. The standard treatment has about an 80% chance of clearing genotype 2 Hepatitis C. It has a 40-45% chance to clear genotype 1 Hepatitis C. The drug most likely to be approved next is Telaprevir, a protease inhibitor (Boceprevir, a similar protease inhibitor is supposedly not far behind). Telaprevir has demonstrated in research testing that, in combination with interferon and ribavirin, it has a genotype 1 clearance rate of about 60-65% (Boceprevir has similar test results). On the surface the reasons for waiting for the new drugs are clear-cut, 60% is a much better chance than 40%. There are a lot of other factors to consider before pinning one’s hopes on the next best thing, however.
First is the discovery of variations in the IL28B gene and how these variations affect response to treatment. If you have the CC variant of the gene, the evidence indicates that your chances of responding well to standard treatment rise to the 60% level, or about the same as the telaprevir response rates. The test to determine which variant you have is available, not extremely expensive and clearly gives information you can use to make a decision about treatment. For a more info the link is here.
Secondly, the new drugs are not assured of either approval or timeliness. The latest Telaprevir application was submitted to the FDA in November, 2010 which means a decision is 6 to 10 months away. Boceprevir has not even reached the “it’s coming in the next x months stage of rumor yet.” There is also the, admittedly small, chance that Telaprevir is never approved. I have many friends who are in the gene-splicing and drug development fields who report a number of instances when companies were extremely confident of FDA approval only to be turned down during the final application. The FDA might come back with concerns that require further testing or additional data submissions, all of which could move the timeline much further out. The promising new polymerase inhibitors (RG7128 and RO5024048 for example) are only just beginning phase II trials which means they are at least 3-5 years away from any sort of approval and only if they succeed in further trials. There are other drugs even further away, etc.
Thirdly, these new drugs are expensive. They project to be about twice as expensive as the current interferon and ribavirin. The plan is that you only need 24 weeks of treatment, but it will be a very expensive 24 weeks. Therefore the question of once the drugs are approved how long it will take for them to be added to insurance company drug formularies so they will be covered by your insurance becomes extremely important. As we all know, insurance companies can be quite recalcitrant about approving new therapies.
Finally, there are all the considerations about your personal situation. What stage is your liver disease? What is your viral load? What is your general health? How old are you? These questions only start to list your issues. What is your financial situation? What is your insurance coverage? What is your work situation? Do you have solid family support? If you have to go on disability, how would that affect your job future? Can you even tell your employer, family, friends and coworkers that you have the disease? All of these and more are considerations that may be more important than the rates of viral response of the various drugs.
Remember two things as think about all the ramifications of when and how to deal with your Hepatitis C: first, there is always a newer, shinier, more promising therapy in the future and second, the best is the enemy of the good.
Last Tuesday was the annual Holiday Pot Luck for the twice-monthly Hepatitis C support group that meets in the California Pacific Medical Center Pathology Conference room. There were about two dozen people there and, in the tradition of potluck dinners everywhere, enough food for twice that number. Best of all, there were plenty of desserts.
Of the two dozen people or so people attending, about half were either currently in treatment or had successfully completed treatment; another quarter had undergone treatment and either failed to respond or the virus had reappeared after the completion of treatment and the last quarter had yet to make a decision about treatment. About half the folks who had successfully completed treatment and never had a recurrence of the virus were people with Hepatitis C genotype 2. This genotype has about an 80% chance of clearance, and excellent prospects of a sustained viral response, with 24 weeks of standard interferon and ribavirin treatment.
After people had settled down with their plates of food and glasses of non-alcoholic libations (ginger potions of all sorts were quite popular), everyone reported on their general state of health, how they felt and any significant issues they had that might be caused or intensified by the disease or their treatment status. Several common themes emerged as people told their stories.
The people who had successfully completed treatment reported that by and large they felt they were back to normal functioning (one individual reported that she felt that after 2 years she still did not feel she was back to her previous cognitive function level). They felt their energy had returned, they no longer had shortness of breath, their strength was back and generally they were physically in good condition. Most felt that their mental faculties and their memory had returned to pre-treatment levels as well. To a person, they reported that it took considerably longer to return to full function than the time that is considered standard by the medical establishment. The usually quoted time to recover from the effects of interferon, ribavirin and the other associated drugs used in treatment is 3 to 6 months. Everyone reported that the time it took them to recover from treatment was in the range of 6 months to 1 year with a few reporting longer times than that.
The people currently in treatment (and for that matter, the folks who had completed treatment) reported two side effects as most debilitating: fatigue and brain fog. The fatigue ranged from merely difficult to extreme with no one reporting only mild fatigue. That said, person after person stated that the most irritating and frustrating side effect was the cognitive deficit associated with interferon brain fog. It was not just the increased memory difficulties, it was the inability to concentrate, the ease of distraction, the loss of train of thought that drove everyone crazy. Most folks also reported nausea of varying degrees, insomnia, sweats etc.; but those paled in comparison to the frustration of brain fog and the annoyance of being tired all the time.
The rest of the people at the meeting, the non-responders to treatment and the people yet to attempt treatment, all had the same outlook: they were waiting for the new and better drugs to become available. They had very different reasons for this viewpoint, but it was surprising to see the uniformity of their point of view.
The non-responders and fail-to-sustainers had all failed at the standard interferon and ribavirin treatment. They and their doctors had come to the conclusion that the two drug standard treatment was not going to successfully defeat the virus in their bodies. They need the additional punch of one of the new drugs in order to have a real chance at success. You can’t argue with that conclusion, when what is available has failed, you have to await further developments to move forward.
The people who had not done any treatment had different reasons for waiting for the next new and better drugs. Many were afraid of the side effects but most were looking for a therapy with a better chance of success that the standard therapy. The standard treatment has about an 80% chance of clearing genotype 2 Hepatitis C. It has a 40-45% chance to clear genotype 1 Hepatitis C. The drug most likely to be approved next is Telaprevir, a protease inhibitor (Boceprevir, a similar protease inhibitor is supposedly not far behind). Telaprevir has demonstrated in research testing that, in combination with interferon and ribavirin, it has a genotype 1 clearance rate of about 60-65% (Boceprevir has similar test results). On the surface the reasons for waiting for the new drugs are clear-cut, 60% is a much better chance than 40%. There are a lot of other factors to consider before pinning one’s hopes on the next best thing, however.
First is the discovery of variations in the IL28B gene and how these variations affect response to treatment. If you have the CC variant of the gene, the evidence indicates that your chances of responding well to standard treatment rise to the 60% level, or about the same as the telaprevir response rates. The test to determine which variant you have is available, not extremely expensive and clearly gives information you can use to make a decision about treatment. For a more info the link is here.
Secondly, the new drugs are not assured of either approval or timeliness. The latest Telaprevir application was submitted to the FDA in November, 2010 which means a decision is 6 to 10 months away. Boceprevir has not even reached the “it’s coming in the next x months stage of rumor yet.” There is also the, admittedly small, chance that Telaprevir is never approved. I have many friends who are in the gene-splicing and drug development fields who report a number of instances when companies were extremely confident of FDA approval only to be turned down during the final application. The FDA might come back with concerns that require further testing or additional data submissions, all of which could move the timeline much further out. The promising new polymerase inhibitors (RG7128 and RO5024048 for example) are only just beginning phase II trials which means they are at least 3-5 years away from any sort of approval and only if they succeed in further trials. There are other drugs even further away, etc.
Thirdly, these new drugs are expensive. They project to be about twice as expensive as the current interferon and ribavirin. The plan is that you only need 24 weeks of treatment, but it will be a very expensive 24 weeks. Therefore the question of once the drugs are approved how long it will take for them to be added to insurance company drug formularies so they will be covered by your insurance becomes extremely important. As we all know, insurance companies can be quite recalcitrant about approving new therapies.
Finally, there are all the considerations about your personal situation. What stage is your liver disease? What is your viral load? What is your general health? How old are you? These questions only start to list your issues. What is your financial situation? What is your insurance coverage? What is your work situation? Do you have solid family support? If you have to go on disability, how would that affect your job future? Can you even tell your employer, family, friends and coworkers that you have the disease? All of these and more are considerations that may be more important than the rates of viral response of the various drugs.
Remember two things as think about all the ramifications of when and how to deal with your Hepatitis C: first, there is always a newer, shinier, more promising therapy in the future and second, the best is the enemy of the good.
Thursday, October 21, 2010
Undetectable
There is a certain sort of mild agony that accompanies waiting for medical test results. You want to know the results, but at the same time you don’t want to learn anything negative. It is a feeling of “please let me know the results as quickly as possible, but only if it is good news.” If the results are delayed, the tension slowly increases until you don’t care what the results are; you just want to hear something definite. I was in that holding pattern until yesterday when I finally got the first viral load numbers I have seen in a month. The tension turned to relief when I learned I was back to undetectable.
Finally, after 16 weeks of Standard of Care chemo, I am officially back to where I was after 6 weeks of the RO5024048 study. I have definitely been undetectable (under 43 IU/ml by this test) since October 6th. I may have been undetectable since September 23rd, but that was the test the lab screwed up. This means that, among other things, my liver is getting a break from the tissue damage that occurs while fighting the Hep C virus. It can begin to heal and regenerate once again.
It also means there is now a date certain (as the politicians would say) for the end of my Standard of Care chemotherapy. The hepatologists at California Pacific Medical Center (CPMC) continue interferon and ribavirin therapy for 36 weeks after the patient reaches undetectable level. That means that June 15th, 2011 will be the end of treatment. Now I can start crossing off weeks on my calendar (or maybe I can start carving marks into my desktop for each week completed) until it is over.
This is all based on the fact that I stay undetectable in each test from now until then, but I have even more motivation now to adhere as closely as possible to the “Best Practices” of the chemo regimen. (Sorry for the corporate terminology in the last sentence, but I was at our strategic planning staff meeting today where I was bombarded with bureaucratic mumblespeak up to and including “creating cross-functional workgroup plans”)
I have a deadline. There is real evidence that the interferon and ribavirin regimen is working. I will hold these facts in front of me like talismans whenever the night sweats get too wet, nothing seems worth eating and getting up the steps of the stadium to the cheap seats leaves me exhausted. It is working and there is an end in sight. It was worth the wait to hear those things.
Finally, after 16 weeks of Standard of Care chemo, I am officially back to where I was after 6 weeks of the RO5024048 study. I have definitely been undetectable (under 43 IU/ml by this test) since October 6th. I may have been undetectable since September 23rd, but that was the test the lab screwed up. This means that, among other things, my liver is getting a break from the tissue damage that occurs while fighting the Hep C virus. It can begin to heal and regenerate once again.
It also means there is now a date certain (as the politicians would say) for the end of my Standard of Care chemotherapy. The hepatologists at California Pacific Medical Center (CPMC) continue interferon and ribavirin therapy for 36 weeks after the patient reaches undetectable level. That means that June 15th, 2011 will be the end of treatment. Now I can start crossing off weeks on my calendar (or maybe I can start carving marks into my desktop for each week completed) until it is over.
This is all based on the fact that I stay undetectable in each test from now until then, but I have even more motivation now to adhere as closely as possible to the “Best Practices” of the chemo regimen. (Sorry for the corporate terminology in the last sentence, but I was at our strategic planning staff meeting today where I was bombarded with bureaucratic mumblespeak up to and including “creating cross-functional workgroup plans”)
I have a deadline. There is real evidence that the interferon and ribavirin regimen is working. I will hold these facts in front of me like talismans whenever the night sweats get too wet, nothing seems worth eating and getting up the steps of the stadium to the cheap seats leaves me exhausted. It is working and there is an end in sight. It was worth the wait to hear those things.
Thursday, September 16, 2010
Latest Viral Load Count – So Close…
When I checked the mailbox on the way home from work today, the envelope with my latest test results was there. The other two envelopes were my paycheck and my wife’s paycheck, but I didn’t register that until later. I wasn’t thinking about money. The only thing I was thinking about was whether those results would show my viral load was undetectable.
In situations like these (preparing to open the envelope bearing important news), you find that you’re still mentally a primitve creature. I’m not a god-botherer, as the Brits would say, but as I walked in the house I was chanting to myself, “Yes, this is it. Please be undetectable. Yes, this is the week. Come on, let’s see undetectable results.” I sat down at the kitchen table (okay, it was the table on the back porch but you get the picture), held the envelope, took a deep breath and opened it up.
My viral load numbers since the viral breakthrough have been: 40.000; 10,000; 5,000; 1,500; 990; 310 and 110 IU/ml. I was really hoping that I would get that final bump down but it didn’t quite happen. The number was 60 IU/ml. Undetectable on this test is 43. It’s been 13 weeks since I went back on full interferon dosing after the breakthrough and I’m not quite there yet. Seventeen of those little bits of viral DNA per milliliter are still hanging on in various nooks and crannies of my bloodstream.
Objectively, this is not the best news. The longer it takes you to reach undetectable levels the lower your percentage of having a sustained viral response at the end of your chemotherapy. But I’m going to keep the same attitude that I had at the beginning of the RO5024048 polymerase inhibitor trial just under ten months ago. Back then I refused to believe that I would not get the test drug and would end up in the placebo arm of the trial. Now, I refuse to believe that I will not be one of the 25% or so who obtain an SVR as slower responders.
I’m not as stubborn as my wife’s Irish ancestry allows her to be, but I have my own stubborn Polish fatalism going for me and I’m going to ride it to the finish. Primitive mentality yes, but it’s the only one I have.
In situations like these (preparing to open the envelope bearing important news), you find that you’re still mentally a primitve creature. I’m not a god-botherer, as the Brits would say, but as I walked in the house I was chanting to myself, “Yes, this is it. Please be undetectable. Yes, this is the week. Come on, let’s see undetectable results.” I sat down at the kitchen table (okay, it was the table on the back porch but you get the picture), held the envelope, took a deep breath and opened it up.
My viral load numbers since the viral breakthrough have been: 40.000; 10,000; 5,000; 1,500; 990; 310 and 110 IU/ml. I was really hoping that I would get that final bump down but it didn’t quite happen. The number was 60 IU/ml. Undetectable on this test is 43. It’s been 13 weeks since I went back on full interferon dosing after the breakthrough and I’m not quite there yet. Seventeen of those little bits of viral DNA per milliliter are still hanging on in various nooks and crannies of my bloodstream.
Objectively, this is not the best news. The longer it takes you to reach undetectable levels the lower your percentage of having a sustained viral response at the end of your chemotherapy. But I’m going to keep the same attitude that I had at the beginning of the RO5024048 polymerase inhibitor trial just under ten months ago. Back then I refused to believe that I would not get the test drug and would end up in the placebo arm of the trial. Now, I refuse to believe that I will not be one of the 25% or so who obtain an SVR as slower responders.
I’m not as stubborn as my wife’s Irish ancestry allows her to be, but I have my own stubborn Polish fatalism going for me and I’m going to ride it to the finish. Primitive mentality yes, but it’s the only one I have.
Sunday, July 25, 2010
Standard of Care Pace vs. Research Pace
I just got my latest viral load numbers back from the lab today. The viral load has declined to just a bit over 1500 I.U./ml. I have now achieved a log level reduction in viral load since the peak of the viral breakthrough. This is great news but also points up one of the biggest differences between being on the Standard of Care treatment of interferon and Ribavirin and the research trial treatment of interferon, Ribavirin and Polymerase Inhibitor RO5024048. The Hep C virus is definitely harder to kill on only two drugs instead of three.
My viral load progression on Standard of Care has been:
Week 1: 40,000 IU/ml. (peak number of viral breakthrough)
Week 2: 10,000 IU/ml
Week 5: 5,000 IU/ml
Week 7: 1,500 IU/ml (log 1.6 reduction)
My viral load progression on the Research Trial drug was:
Week 0: 12,900,000 IU/ml.
Week 1: 4,260 IU/ml (log 3.48 reduction)
Week 2: 1,110 IU/ml
Week 4: 195 IU/ml
Week 6: undetectable (log 5.83 reduction)
As you can see, the pace at which the virus is destroyed is much slower (though steady) on the interferon and Ribavirin combination. It has taken 6 weeks to get a log 1.6 reduction from the peak breakthrough number when it only took one week to get a log 3.5 reduction from my pre-trial viral load on the polymerase inhibitor. This has taken some getting used to. You get spoiled on the three drug therapy, especially in the case of the polymerase inhibitor because it does not seem to carry major additional side effects along with it. While I steadily heading towards the log 2 reduction in my viral load needed by week twelve after the breakthrough in order to continue treatment, it seems to be happening in slow motion after the knockout blow the RO5024048 dealt the virus while I was on the three drug combination.
While this may pose a few psychological issues for me to deal with, the overall outlook for the polymerase inhibitor plus interferon and Ribavirin mode of treatment is very good. It definitely deals a hammer blow to the virus and so far, most of the individuals I have talked to who are in the trial (admittedly a very small sample) have not reported serious side effects associated with the RO5024048. Also the addition of a new group to the trial which will receive the drug for 24 weeks instead of the 8-12 weeks we got it indicates that the safety issues are not a major concern and that the drug is promising enough to expand the range of patients eligible. This is all very good news for people both awaiting treatment and considering their treatment options. Another effective tool appears to be on the way in the battle against the Hep C virus.
My viral load progression on Standard of Care has been:
Week 1: 40,000 IU/ml. (peak number of viral breakthrough)
Week 2: 10,000 IU/ml
Week 5: 5,000 IU/ml
Week 7: 1,500 IU/ml (log 1.6 reduction)
My viral load progression on the Research Trial drug was:
Week 0: 12,900,000 IU/ml.
Week 1: 4,260 IU/ml (log 3.48 reduction)
Week 2: 1,110 IU/ml
Week 4: 195 IU/ml
Week 6: undetectable (log 5.83 reduction)
As you can see, the pace at which the virus is destroyed is much slower (though steady) on the interferon and Ribavirin combination. It has taken 6 weeks to get a log 1.6 reduction from the peak breakthrough number when it only took one week to get a log 3.5 reduction from my pre-trial viral load on the polymerase inhibitor. This has taken some getting used to. You get spoiled on the three drug therapy, especially in the case of the polymerase inhibitor because it does not seem to carry major additional side effects along with it. While I steadily heading towards the log 2 reduction in my viral load needed by week twelve after the breakthrough in order to continue treatment, it seems to be happening in slow motion after the knockout blow the RO5024048 dealt the virus while I was on the three drug combination.
While this may pose a few psychological issues for me to deal with, the overall outlook for the polymerase inhibitor plus interferon and Ribavirin mode of treatment is very good. It definitely deals a hammer blow to the virus and so far, most of the individuals I have talked to who are in the trial (admittedly a very small sample) have not reported serious side effects associated with the RO5024048. Also the addition of a new group to the trial which will receive the drug for 24 weeks instead of the 8-12 weeks we got it indicates that the safety issues are not a major concern and that the drug is promising enough to expand the range of patients eligible. This is all very good news for people both awaiting treatment and considering their treatment options. Another effective tool appears to be on the way in the battle against the Hep C virus.
Wednesday, July 14, 2010
RO5024048 Side Effects Reconsidered
Now that I am out of the study and on the Standard of Care of Interferon and Ribavirin, I have been looking back at the first 8 to 12 weeks of treatment to try to determine whether the RO5024048 polymerase inhibitor had side effects of its own, whether it intensified the side effects of the interferon and Ribavirin or did both.
As I have mentioned before in this post, I believe I received the study drug at the beginning of treatment. My viral load dropped log 3.6 or so during the first week of the drug trial, which is almost unheard of on the standard of care. I have yet to drop a full log number from the peak viral load after my viral breakthrough 5 weeks ago now that I am on Standard of Care treatment. This just reinforces my belief that I was given RO5024048. That said, I do not know either how long I received the study drug, nor the size of the dose I received. I could have received 500 mg for 12 weeks, 1000 mg for 12 weeks, or 1000 mg for 8 weeks. In any case, I believe I received the polymerase inhibitor for either the first 8 weeks or the first 12 weeks of the study.
Looking at the list of side effects from the drugs involved I can draw some conclusions about the variation in them as the study went on.
Nausea: seems about the same throughout the study, mild but occasionally intrusive
Vomiting: only happened once
Diarrhea: definitely more serious at the beginning of the study and gradually disappeared as the study went on
Abdominal Pain: is more noticeable in the past 8 weeks
Anorexia: I don’t believe I had it
Dysgeusia: Didn’t notice it until about 8 weeks into treatment
Dry Mouth & Dyspepsia: consistently present throughout treatment
Anemia: seems worse now that I am on standard of care
Neutropenia: set in about 8 weeks into the study and has been consistently present since
Fatigue: seems a bit better since I have been on only interferon and Ribavirin
Chills: present the first several weeks of the trial has disappeared since
Fever: cyclic with the interferon injection schedule throughout the trial
Muscle Pain: intermittently present throughout treatment up to the present, also a general feeling of muscle weakness and fatigue after exertion
Joint Pain: present during the first few months of the trial not present now
Headache: present throughout the trial, more intense early in the trial and during the past 5 weeks
Rash: Never a big problem, but more noticeable during the first few months
Dizziness: only when taking some of the ancillary drugs
Anxiety: peaked during weeks 12-18
Depression: peaked during weeks 10-18
Insomnia: consistently present throughout treatment
Irritability: very irritable early in the trial, became a problem again in weeks 12-18, not a problem since introduction of antidepressants
Throat Pain: have not had any
Injection Site Redness: has not appeared at any time
Sinus Congestion: tends to occur during the first 4 or 5 days after each interferon injection
Alopecia: Hair loss consistent through first 20 weeks of treatment, has moderated since
Blurred Vision: not specifically noticed, but my close focusing ability deteriorated immediately at the start of the trial and the deterioration has remained
Eye Pain: have consistently had eye pain. It tends to happen when attempting to focus on something relatively close to my eyes. Generally moderates when I relax my eyes and my focus
Blood Sugar Problems: none
Back Pain: tightness occurs within a few days of every interferon injection
Laryngitis: none
Sore Throat: has occurred intermittently since the start treatment
Loss of Concentration: As the treatment progressed, my ability to concentrate noticeably declined at about 2:30 every day
Confusion: my short term memory has declined noticeably since the start of treatment
Liver Problems: I developed a hypothyroid condition starting at about week 10
As I look over the list of side effects I notice only a few that seem like they could be directly related to the RO5024048. Diarrhea is something that was only a problem during the time I was on the test drug. Chills have not really happened since the first 8 weeks either. Fatigue seems to have been amplified a bit by the polymerase inhibitor. Joint pain also seemed to disappear after the first 8-10 weeks of the trial. The rash problem was never more than an annoyance and was more extensive during the first 8 weeks. Irritability was definitely high at the beginning of the trial and has moderated since them, particularly since taking the antidepressants. The vision change happened right away, but I also noticed that there was a bit of change to it when I went back on full interferon doses 5 weeks ago.
Most of these are also side effects of the interferon and Ribavirin so the fact that they have moderated over time might just be that my body acclimated to the drugs. If I had to make the call, I would say that diarrhea, joint pain fatigue and rash were all either caused by or intensified by the RO5024048. It seems that the polymerase inhibitor is an easier to tolerate drug that the protease inhibitors such as Telaprevir and Boceprevir. The research coordinators I talked to all said that the Telaprevir study they had run had been much harder on the patients in terms of side effects (especially rash) than the RO5024048.
Given that it seems to hit the virus like the blitzkrieg hit Poland and that it appears to have a more moderate level of side effects than some of the other new drugs, RO5024048 seems to have a bright future fighting Hepatitis C.
As I have mentioned before in this post, I believe I received the study drug at the beginning of treatment. My viral load dropped log 3.6 or so during the first week of the drug trial, which is almost unheard of on the standard of care. I have yet to drop a full log number from the peak viral load after my viral breakthrough 5 weeks ago now that I am on Standard of Care treatment. This just reinforces my belief that I was given RO5024048. That said, I do not know either how long I received the study drug, nor the size of the dose I received. I could have received 500 mg for 12 weeks, 1000 mg for 12 weeks, or 1000 mg for 8 weeks. In any case, I believe I received the polymerase inhibitor for either the first 8 weeks or the first 12 weeks of the study.
Looking at the list of side effects from the drugs involved I can draw some conclusions about the variation in them as the study went on.
Nausea: seems about the same throughout the study, mild but occasionally intrusive
Vomiting: only happened once
Diarrhea: definitely more serious at the beginning of the study and gradually disappeared as the study went on
Abdominal Pain: is more noticeable in the past 8 weeks
Anorexia: I don’t believe I had it
Dysgeusia: Didn’t notice it until about 8 weeks into treatment
Dry Mouth & Dyspepsia: consistently present throughout treatment
Anemia: seems worse now that I am on standard of care
Neutropenia: set in about 8 weeks into the study and has been consistently present since
Fatigue: seems a bit better since I have been on only interferon and Ribavirin
Chills: present the first several weeks of the trial has disappeared since
Fever: cyclic with the interferon injection schedule throughout the trial
Muscle Pain: intermittently present throughout treatment up to the present, also a general feeling of muscle weakness and fatigue after exertion
Joint Pain: present during the first few months of the trial not present now
Headache: present throughout the trial, more intense early in the trial and during the past 5 weeks
Rash: Never a big problem, but more noticeable during the first few months
Dizziness: only when taking some of the ancillary drugs
Anxiety: peaked during weeks 12-18
Depression: peaked during weeks 10-18
Insomnia: consistently present throughout treatment
Irritability: very irritable early in the trial, became a problem again in weeks 12-18, not a problem since introduction of antidepressants
Throat Pain: have not had any
Injection Site Redness: has not appeared at any time
Sinus Congestion: tends to occur during the first 4 or 5 days after each interferon injection
Alopecia: Hair loss consistent through first 20 weeks of treatment, has moderated since
Blurred Vision: not specifically noticed, but my close focusing ability deteriorated immediately at the start of the trial and the deterioration has remained
Eye Pain: have consistently had eye pain. It tends to happen when attempting to focus on something relatively close to my eyes. Generally moderates when I relax my eyes and my focus
Blood Sugar Problems: none
Back Pain: tightness occurs within a few days of every interferon injection
Laryngitis: none
Sore Throat: has occurred intermittently since the start treatment
Loss of Concentration: As the treatment progressed, my ability to concentrate noticeably declined at about 2:30 every day
Confusion: my short term memory has declined noticeably since the start of treatment
Liver Problems: I developed a hypothyroid condition starting at about week 10
As I look over the list of side effects I notice only a few that seem like they could be directly related to the RO5024048. Diarrhea is something that was only a problem during the time I was on the test drug. Chills have not really happened since the first 8 weeks either. Fatigue seems to have been amplified a bit by the polymerase inhibitor. Joint pain also seemed to disappear after the first 8-10 weeks of the trial. The rash problem was never more than an annoyance and was more extensive during the first 8 weeks. Irritability was definitely high at the beginning of the trial and has moderated since them, particularly since taking the antidepressants. The vision change happened right away, but I also noticed that there was a bit of change to it when I went back on full interferon doses 5 weeks ago.
Most of these are also side effects of the interferon and Ribavirin so the fact that they have moderated over time might just be that my body acclimated to the drugs. If I had to make the call, I would say that diarrhea, joint pain fatigue and rash were all either caused by or intensified by the RO5024048. It seems that the polymerase inhibitor is an easier to tolerate drug that the protease inhibitors such as Telaprevir and Boceprevir. The research coordinators I talked to all said that the Telaprevir study they had run had been much harder on the patients in terms of side effects (especially rash) than the RO5024048.
Given that it seems to hit the virus like the blitzkrieg hit Poland and that it appears to have a more moderate level of side effects than some of the other new drugs, RO5024048 seems to have a bright future fighting Hepatitis C.
Thursday, June 17, 2010
The Rest of the Story…
What really happened when I formally left the study was, needless to say, much less histrionic, though it had its own brand of drama.
I got a call from AVB in the morning announcing the lab results were back, I had a confirmed viral breakthrough and I had to stop taking the meds belonging to the research study. She was working on getting some medical samples from the Roche representative that would bridge me over until my insurance authorizations went through and my prescriptions for Pegasys and Ribavirin were filled. She told me that when she had some news she would contact me and then I could bring my old meds in and get the bridge meds from her.
Sure enough the call came through at 3:00 p.m. that same day while I was in an event planning meeting. She had arranged the bridge meds and could I get to the hepatology research center no later than 4:30 to pick them up and drop off the old stuff. I was without transportation, but promised to do my best. I excused myself from the meeting by telling everyone I had to go pick up drugs and started walking quickly the 1 ½ miles to my home.
As anyone in San Francisco who relies on the Municipal Railroad system, or MUNI as it is infamously known, schedules are something that are mostly honored in their breach. I walked the distance home along a MUNI route without seeing a bus during the entire 40 minutes. I grabbed my meds, diary, sharps container and fanny pack jumped in my trusty pickup and headed back toward the research center. I went back over the same route and still did not see a bus by the time I had to turn off on other streets.
When I got to the center, I met AVB and she collected my old meds and other materials. I actually got to keep my Roche Logowear. She explained that she had samples of Ribavirin and Pegasys that should tide me over until the insurance authorizations cleared and that she was on her way to Dr. B’s office (who had stayed late to be available) to get the necessary documents signed. She returned with the meds and with the gentleman who would be the nurse coordination for my treatment with Dr. B. She introduced us; he gave me his contact info and he told me he would be in touch with a day or two to follow up on the authorization status. He gave me some lab test request sheets and a preliminary schedule of when I needed to get lab tests done. The he shook my hand and, wished me good luck and said he would contact me soon.
AVB then went over the kit of materials that is given to outpatient treatment subjects and showed me how to use the preloaded syringes that the Pegasys came in. No more vials to fill syringes from, Yay!
At that point she wished me good luck, said that she was still available as well if I had questions or needed to go over any of my previous history on the study. She choked up a bit. I choked up a bit. I thanked her for all the efforts she had made on my behalf, she said don’t worry about that now, just work on having a successful treatment. We shook hands and she put her arm on my shoulder and walked me down the hall to say good-bye.
And that’s the Rest Of The Story…(apologies to Paul Harvey)
Wednesday, June 16, 2010
Drummed Out of the Study
The confirmatory test results came in and I got the phone call from AVB formally telling me that I had a viral breakthrough and as per the protocols of the research trial must be taken off research treatment. I was asked to come in with my unused meds and my records.
I gathered together my bottles of Ribavirin both empty and full, my sharps container with all my used syringes, my unused vials of interferon in my insulated Roche fanny pack, my diary with records of the timing and amount of my daily doses of meds, loaded them into a bag and drove to the CPMC hepatology research center.
I trudged, gasping, up the hill to the hospital, rode alone in the clanking elevator to the third floor and was escorted into one of the closet-sized examining rooms. I stood in front of the desk of research coordinator AVB and unloaded my bag. The vials were counted, the pills were counted, the sharps container set aside for the later counting of the used syringes and my never-to-be completed dosing diary was confiscated from me. The Roche logo was ceremoniously cut off my insulated fanny-pack and it was tossed back to me. I was slapped on each cheek with the partially completed diary and as the theme song to Branded played in the background I was marched out of the room. As I walked down the hallway towards the elevator the nurses averted their eyes, the lab tech closed his door and the other patients behaved as though I did not exist. The walk back to my truck became another endless, gasping, uphill climb. What shreds of my dignity I had managed to preserve until that time broke down when I got into my vehicle and I sobbed uncontrollably over the steering wheel until I could gather what composure I could and drive back across the pitiless city to my cold, echoing home.
Tomorrow…The Rest of The Story.
I gathered together my bottles of Ribavirin both empty and full, my sharps container with all my used syringes, my unused vials of interferon in my insulated Roche fanny pack, my diary with records of the timing and amount of my daily doses of meds, loaded them into a bag and drove to the CPMC hepatology research center.
I trudged, gasping, up the hill to the hospital, rode alone in the clanking elevator to the third floor and was escorted into one of the closet-sized examining rooms. I stood in front of the desk of research coordinator AVB and unloaded my bag. The vials were counted, the pills were counted, the sharps container set aside for the later counting of the used syringes and my never-to-be completed dosing diary was confiscated from me. The Roche logo was ceremoniously cut off my insulated fanny-pack and it was tossed back to me. I was slapped on each cheek with the partially completed diary and as the theme song to Branded played in the background I was marched out of the room. As I walked down the hallway towards the elevator the nurses averted their eyes, the lab tech closed his door and the other patients behaved as though I did not exist. The walk back to my truck became another endless, gasping, uphill climb. What shreds of my dignity I had managed to preserve until that time broke down when I got into my vehicle and I sobbed uncontrollably over the steering wheel until I could gather what composure I could and drive back across the pitiless city to my cold, echoing home.
Tomorrow…The Rest of The Story.
Saturday, June 12, 2010
Bad News is Not So Bad 2
The Kindness of Doctors.
All of us who have being living in the American health care system have stories of the system letting people down. Doctors who sleepwalk through their job; insurance companies that find any way possible to deny care; nurses who are surly and hostile; hospitals that warehouse and ignore patients. After a lifetime of these kinds of events, you can become fairly cynical about the motives of healthcare professionals and about their dedication to their jobs and those under their care. The response that has been shown by the folks in the Roche RO5024048 study is the kind of event that can restore your faith in doctors.
In the first phone call to me informing me that I had had a viral breakthrough, AVB the study coordinator told me that I should ask Doctor B, the hepatologist, what she thought about my continuing treatment outside the study protocol. She said there were no guarantees, but I should certainly ask the question. I did not have a lot of confidence in Doctor B’s response. She is the lead doctor on the study. She gets her name on the research paper written about the study and in the interests of gaining research data for the study putting me off-protocol does not help her do that.
When we had our meeting just after the retest blood draws, she went over the viral breakthrough test results and mentioned that, subject to the results of these tests, I would be off the research treatments. AVB mentioned that I had a question for her and I asked about continuing treatment outside the study. Doctor B wanted to look at me test results and most particularly my dosing record. We she examined them in detail and saw that the breakthrough had occurred after 2 skipped doses of interferon due to low neutrophil counts and that I had been on a reduced interferon dose for several weeks before that, her whole personal affect changed. It was a subtle shift from researcher to doctor. She looked closely at my viral load numbers and saw that I had been undetectable for between 12 and 18 weeks even on the reduced dosing and that the dose reductions had all been due to low neutrophil counts (neutropenia). She asked me how I had been handling treatment and the treatment side effects. She told me that outside the research study protocol, she could administer drugs to combat both the neutropenia and the lowered hemoglobin counts. This would allow me to have a good chance to continue treatment on the full doses of interferon and ribavirin, thus giving me the best chance to clear the virus. She mentioned that other drugs were in the pipeline and nearing approval, particularly telaprevir, and did I think I wanted to wait or to continue with treatment now.
I told her I was leaning toward continuing treatment now, but wanted to talk to doctor C, my gastroenterologist before I made my final decision. She immediately told me that she would call him and let him know the latest situation and that I should talk to him and my primary care person as soon as possible so as to be able to get the treatment drug approval process under way with the insurance company as soon as possible. She also volunteered to oversee my treatment if I got a referral to her from my primary care doctor. She also volunteered to call him as well and let him know the situation.
To see the change in view from research scientist to medical doctor determining the best course of care for her patient caught me completely off-guard. It seemed to occur in a matter of an eye-blink. She became completely focused on letting me know the options and the possibilities. It gives me a great deal of confidence in having her as my hepatologist going forward.
My conversation with Doctor C was similar. He wanted to know if I felt I could handle treatment going forward. He also wanted me to know that the percentages of clearing after an event like this are not high. He also emphasized the availability of the drugs to treat the low blood cell counts and the fact that this would allow the higher doses of the Hep C Standard of Care drugs. But the decision is always in my hands.
I am going forward with treatment. It may take a few weeks to get everything set up, but the test results don’t come back until after my usual dosing schedule, so I will have one last dose in my from the Roche study before I forge ahead on my own.
Just as a final note and reality check, I had a meeting with my primary Doctor K. I have some thyroid function issues due to treatment and he needed to prescribe something for that and issue the referral to Doctor B for insurance company purposes. Ah, the reality of being back in the arms of my overworked primary care doctor. Listen, no chance, talk over me, of course, give me confusing instructions, par for the course. It’s good to know something things don’t change…
All of us who have being living in the American health care system have stories of the system letting people down. Doctors who sleepwalk through their job; insurance companies that find any way possible to deny care; nurses who are surly and hostile; hospitals that warehouse and ignore patients. After a lifetime of these kinds of events, you can become fairly cynical about the motives of healthcare professionals and about their dedication to their jobs and those under their care. The response that has been shown by the folks in the Roche RO5024048 study is the kind of event that can restore your faith in doctors.
In the first phone call to me informing me that I had had a viral breakthrough, AVB the study coordinator told me that I should ask Doctor B, the hepatologist, what she thought about my continuing treatment outside the study protocol. She said there were no guarantees, but I should certainly ask the question. I did not have a lot of confidence in Doctor B’s response. She is the lead doctor on the study. She gets her name on the research paper written about the study and in the interests of gaining research data for the study putting me off-protocol does not help her do that.
When we had our meeting just after the retest blood draws, she went over the viral breakthrough test results and mentioned that, subject to the results of these tests, I would be off the research treatments. AVB mentioned that I had a question for her and I asked about continuing treatment outside the study. Doctor B wanted to look at me test results and most particularly my dosing record. We she examined them in detail and saw that the breakthrough had occurred after 2 skipped doses of interferon due to low neutrophil counts and that I had been on a reduced interferon dose for several weeks before that, her whole personal affect changed. It was a subtle shift from researcher to doctor. She looked closely at my viral load numbers and saw that I had been undetectable for between 12 and 18 weeks even on the reduced dosing and that the dose reductions had all been due to low neutrophil counts (neutropenia). She asked me how I had been handling treatment and the treatment side effects. She told me that outside the research study protocol, she could administer drugs to combat both the neutropenia and the lowered hemoglobin counts. This would allow me to have a good chance to continue treatment on the full doses of interferon and ribavirin, thus giving me the best chance to clear the virus. She mentioned that other drugs were in the pipeline and nearing approval, particularly telaprevir, and did I think I wanted to wait or to continue with treatment now.
I told her I was leaning toward continuing treatment now, but wanted to talk to doctor C, my gastroenterologist before I made my final decision. She immediately told me that she would call him and let him know the latest situation and that I should talk to him and my primary care person as soon as possible so as to be able to get the treatment drug approval process under way with the insurance company as soon as possible. She also volunteered to oversee my treatment if I got a referral to her from my primary care doctor. She also volunteered to call him as well and let him know the situation.
To see the change in view from research scientist to medical doctor determining the best course of care for her patient caught me completely off-guard. It seemed to occur in a matter of an eye-blink. She became completely focused on letting me know the options and the possibilities. It gives me a great deal of confidence in having her as my hepatologist going forward.
My conversation with Doctor C was similar. He wanted to know if I felt I could handle treatment going forward. He also wanted me to know that the percentages of clearing after an event like this are not high. He also emphasized the availability of the drugs to treat the low blood cell counts and the fact that this would allow the higher doses of the Hep C Standard of Care drugs. But the decision is always in my hands.
I am going forward with treatment. It may take a few weeks to get everything set up, but the test results don’t come back until after my usual dosing schedule, so I will have one last dose in my from the Roche study before I forge ahead on my own.
Just as a final note and reality check, I had a meeting with my primary Doctor K. I have some thyroid function issues due to treatment and he needed to prescribe something for that and issue the referral to Doctor B for insurance company purposes. Ah, the reality of being back in the arms of my overworked primary care doctor. Listen, no chance, talk over me, of course, give me confusing instructions, par for the course. It’s good to know something things don’t change…
Wednesday, June 9, 2010
Bad News Is Not So Bad News 1
The situation of having a viral breakthrough and the decisions made about treatment in light of that breakthrough is a good illustration of the differences between undergoing treatment under the protocols of a drug trial and undergoing treatment under the Standard Of Care supervised by a hepatologist. There is a bit about that is this post.
I met with Doctor B, the doctor in charge of the Roche RO5024048 study today. I was getting the blood tests to confirm that I indeed had a viral breakthrough and met with her as part of that process. Given that it would be highly unusual for the tests to show that I was again undetectable, I am going to be dropped from treatment under the protocols of the study (the protocol is that if you show any viral activity at week 24, treatment is suspended). That being the case, I asked Dr. B what her opinion was of the value of my continuing outside the study using the standard interferon and ribavirin treatment.
She was initially noncommittal and wanted to see my viral load history and my dosing history for the Pegasys and ribavirin. She saw that my viral load had been undetectable for 18 weeks. She also saw that I had spent 5 weeks on a ¾ dose of interferon, had skipped 2 doses completely due to low neutrophil counts and had just resumed injecting at a ½ dose level. I had also been on a reduced dose of ribavirin for the past 7 weeks. When she saw that the breakthrough had occurred after the two skipped doses of interferon, she warmed to the idea. She asked me how I have been tolerating the treatment. I told her I had a lot of the usual side effects but that the addition of an antidepressant had really made a huge difference in my mental outlook and my mental energy. Then she pointed out the reasons she thought it might be worthwhile to pursue.
If you undergo treatment under normal circumstances, you can be prescribed drugs to reduce the loss of neutrophils (neutropenia). You can also be prescribed meds to help with the hemoglobin loss as well. They don’t do this in drug trials because they are trying to control the number of variables as well as to determine the effect the study meds are having with the interference of other drugs. Being able to take these additional medications means that the full doses of interferon and ribavirin can be maintained for the longest possible time during the course of treatment. It goes without saying that this increases the chances for a successful outcome.
In my case for about 40 % of the time I have been in the study, I have been taking reduced doses of just those standard medicines that have proven so successful against Hep C. Moving forward with treatment under full doses means I have a chance to reach a successful outcome. Given the 6 months I have spent on this so far, I don’t see why I shouldn’t grab that chance.
I met with Doctor B, the doctor in charge of the Roche RO5024048 study today. I was getting the blood tests to confirm that I indeed had a viral breakthrough and met with her as part of that process. Given that it would be highly unusual for the tests to show that I was again undetectable, I am going to be dropped from treatment under the protocols of the study (the protocol is that if you show any viral activity at week 24, treatment is suspended). That being the case, I asked Dr. B what her opinion was of the value of my continuing outside the study using the standard interferon and ribavirin treatment.
She was initially noncommittal and wanted to see my viral load history and my dosing history for the Pegasys and ribavirin. She saw that my viral load had been undetectable for 18 weeks. She also saw that I had spent 5 weeks on a ¾ dose of interferon, had skipped 2 doses completely due to low neutrophil counts and had just resumed injecting at a ½ dose level. I had also been on a reduced dose of ribavirin for the past 7 weeks. When she saw that the breakthrough had occurred after the two skipped doses of interferon, she warmed to the idea. She asked me how I have been tolerating the treatment. I told her I had a lot of the usual side effects but that the addition of an antidepressant had really made a huge difference in my mental outlook and my mental energy. Then she pointed out the reasons she thought it might be worthwhile to pursue.
If you undergo treatment under normal circumstances, you can be prescribed drugs to reduce the loss of neutrophils (neutropenia). You can also be prescribed meds to help with the hemoglobin loss as well. They don’t do this in drug trials because they are trying to control the number of variables as well as to determine the effect the study meds are having with the interference of other drugs. Being able to take these additional medications means that the full doses of interferon and ribavirin can be maintained for the longest possible time during the course of treatment. It goes without saying that this increases the chances for a successful outcome.
In my case for about 40 % of the time I have been in the study, I have been taking reduced doses of just those standard medicines that have proven so successful against Hep C. Moving forward with treatment under full doses means I have a chance to reach a successful outcome. Given the 6 months I have spent on this so far, I don’t see why I shouldn’t grab that chance.
Saturday, June 5, 2010
Thoughts From The Nail
The shock of having a viral breakthrough is wearing off. I have spent some considerable time today mulling over the implications of the virus returning. For anyone in this situation, there are a number of considerations and possibilities.
Is there something that presents itself as a reason that the breakthrough might have happened? Does it appear to have happened despite your best efforts to adhere to the protocol? If it happened in spite of you taking all you meds correctly, your virus might be developing a resistance to the type of interferon you are taking or to interferon in general. There is evidence that changing the brand of pegylated interferon you are taking can change the results against the virus. You can talk to your doctor about the possibility of changing the type of interferon you are taking. Of course some insurance plans only include one company’s pegylated interferon in their formulary which means you are out of luck unless you have the $500+ per dose to cover the change.
I believe there was a specific reason for my breakthrough. I think it resulted from dose adjustments made to my interferon dose dictated by the study protocols. These dose adjustments happen to many patients who are undergoing treatment. They are made to attempt to control side effects for the most part. If your hemoglobin drops, if your neutrophil or lymphocyte counts drop too far a dose adjustment will be made in your interferon or ribavirin. In my case, they reduced my Ribavirin dose from 1200 mg to 1000 mg per day after a week 16 retest showed my hemoglobin had dropped to 9.6. I don’t think this had much to do with it. More importantly, at week 21 my neutrophil count went down to 360 and I was told to skip my interferon dose. The next week the count had not rebounded quite far enough and I had to skip another dose. I had only injected one time before my week 24 tests and that was a half dose. I think the suspension of my interferon for two weeks directly contributed to the viral breakthrough.
Which way is you viral load trending? If you have a breakthrough, they are going to retest you to reconfirm that it is a real event. It could be a lab error, especially if it just blips a bit over the undetectable level, or it could be a one-time event. If the results show that your breakthrough is real and the viral load is rising, you’ve probably got a resistant virus and will need to change your treatment drugs or dosing. If your breakthrough is real, but the viral load is declining, then the continuation of your present treatment regimen might mean you will return to the undetectable level. If the results show you are again undetectable, then perhaps it was a test error or one-time event and you can curse the additional gray hair you got while waiting for the results.
Is adjusting your dosing possible? If your breakthrough occurred after lowering your doses of medications, is it possible to raise them again and safely manage the side effects? Did the side effects, especially the blood counts, mean you absolutely had to reduce the dose?
Do you have the option of continuing treatment through your own insurance or by funding it yourself, or is being in a study the only way you can afford treatment?
Does a viral breakthrough mean you are starting over from week one of the 48 week treatment regimen or, if your viral load is trending downward again, would it mean only a continuation to the end of the original treatment time-frame?
All these are questions to ponder. You can endlessly mull them over in your mind right away, or you can try to get away from them for a bit and start to obsess about them when your get your retest results.
I tend more toward the drive yourself crazy by obsessing about them continuously camp. Luckily I have a bunch of drugs to calm me down and help me sleep, otherwise by late next week, I would be a mere husk of myself. Try not to go down that path.
They may have dropped the MPSH on me, but even that bounces after it hits you…
Tuesday, April 20, 2010
Week 18 – On A More Personal Note…
Yesterday I passed on the news about the expansion of the RO5024048 combination drug trial. Today I’ll pass on the personal news about my condition.
They did all the usual blood draws (only 14 vials this time), and various vitals but no EKG. I didn’t notice that they were not doing it and therefore never asked why it did not happen. When they checked my weight, it turned out I have lost 12 pounds in the last 8 weeks. I had noticed my belt being a bit loose, but I didn’t think I had lost that much weight. I don’t have the energy to exercise heavily so I guess I am eating less than I think.
I’m still undetectable as of week 14 (which was 4 weeks ago) which is the best news of the day. 8 official weeks of no detectable virus levels is encouraging and definitely helps during the various bouts of side effects. About 3 weeks ago they dropped my Copegus dose to 1000mg from 1200mg per day. My Hemoglobin has popped up very slightly but I am still down 35% over normal. The only new development with the shortness of breath associated with the anemia is that now I occasional get out of breath while talking. Thankfully it only tends to happen when I have to project a bit to be heard in a noisy room or in a large group, the usual day-to-day nattering is unaffected (to the occasional chagrin of those subjected to it). White blood cells are low but just above the cutoff line.
About 3 weeks ago, my neutrophil count increased enough that they restored me to a full dose (180mg) of Pegasys from the 3/4 dose (135 mg) that I had been on for about 6 weeks. This brought back a whole raft of side effects that had moderated during the lower dose of interferon. Headaches, rash with itching (thankfully mild), nausea and more intense insomnia all were once again daily, or at least several times weekly, features of life. I had actually thought that my body had begun to acclimate to the treatment drugs, but with the return of all of these side effects, I believe the lower occurrence was due to the lower dose.
I have been having bouts of insomnia for several weeks and given that they have increased with the increase in my interferon dose, the consulting doctor to the study decided to proscribe trazodone to help me sleep. I have taken it twice and while on the first night it did not seem to help at all, the second night found it working better and I think I got a decent night’s sleep. I will report back on the results in the future.
As for reports, taking acetaminophen instead of ibuprofen, just before my Pegasys (interferon) injection has had no effect on my fatigue in the 24-36 hours after the injection. I feel just as crappy taking Tylenol as I do taking Motrin, so much for the miracles of modern pharmacology.
Time to head out the door to the support group. Best of all, I can listen to the Giants game on the way there and maybe on the way back…if I don’t forget they’re playing before I get to the car.
They did all the usual blood draws (only 14 vials this time), and various vitals but no EKG. I didn’t notice that they were not doing it and therefore never asked why it did not happen. When they checked my weight, it turned out I have lost 12 pounds in the last 8 weeks. I had noticed my belt being a bit loose, but I didn’t think I had lost that much weight. I don’t have the energy to exercise heavily so I guess I am eating less than I think.
I’m still undetectable as of week 14 (which was 4 weeks ago) which is the best news of the day. 8 official weeks of no detectable virus levels is encouraging and definitely helps during the various bouts of side effects. About 3 weeks ago they dropped my Copegus dose to 1000mg from 1200mg per day. My Hemoglobin has popped up very slightly but I am still down 35% over normal. The only new development with the shortness of breath associated with the anemia is that now I occasional get out of breath while talking. Thankfully it only tends to happen when I have to project a bit to be heard in a noisy room or in a large group, the usual day-to-day nattering is unaffected (to the occasional chagrin of those subjected to it). White blood cells are low but just above the cutoff line.
About 3 weeks ago, my neutrophil count increased enough that they restored me to a full dose (180mg) of Pegasys from the 3/4 dose (135 mg) that I had been on for about 6 weeks. This brought back a whole raft of side effects that had moderated during the lower dose of interferon. Headaches, rash with itching (thankfully mild), nausea and more intense insomnia all were once again daily, or at least several times weekly, features of life. I had actually thought that my body had begun to acclimate to the treatment drugs, but with the return of all of these side effects, I believe the lower occurrence was due to the lower dose.
I have been having bouts of insomnia for several weeks and given that they have increased with the increase in my interferon dose, the consulting doctor to the study decided to proscribe trazodone to help me sleep. I have taken it twice and while on the first night it did not seem to help at all, the second night found it working better and I think I got a decent night’s sleep. I will report back on the results in the future.
As for reports, taking acetaminophen instead of ibuprofen, just before my Pegasys (interferon) injection has had no effect on my fatigue in the 24-36 hours after the injection. I feel just as crappy taking Tylenol as I do taking Motrin, so much for the miracles of modern pharmacology.
Time to head out the door to the support group. Best of all, I can listen to the Giants game on the way there and maybe on the way back…if I don’t forget they’re playing before I get to the car.
Monday, April 19, 2010
New Developments in Roche RO5024048 Combination Treatment Drug Trial
I went in last Friday for my week 18 tests. Before we started the usual blood draws, EKG and vital signs routine, there was a new development. There is a change to the study protocols that required signing a new consent form. There had been a previous, minor, change that necessitated my signing a one-sheet addendum to the original consent form, but this change involved major changes and resulted in my having to agree to changes throughout the agreement. The new protocol is very good news for the safety of the drug and offers an additional chance for study under-responders.
What is happening is that Roche is adding another treatment arm to the study. In this arm “The safety and efficacy of open-label HCV polymerase inhibitor Prodrug (RO5024048) in combination with PEG-INF and RBV in the subset of patients who only received currently approved combination of SOC in the main study and who did not demonstrate an early virologic response (Treatment Failures) will be evaluated.” What this means is that the people in the arm of the study that received the SOC (pegylated interferon and ribavirin) and did not receive the experimental drug and who did not have a log 210 reduction in virus after 12 weeks or who had virus still in the blood after 24 weeks and thus had to stop taking all medications will get a shot at receiving the full triple-drug therapy.
The new arm (Group F) will take RO5024048 1000mg twice daily for 24 weeks in combination with the SOC of weekly Pegasys (interferon) and daily Copegus (ribavirin), followed by an additional 24 weeks of the SOC (Pegasys and Copegus). The study will be open-label meaning patients and doctors will know the medications they are receiving.
The best aspect of this new arm being added to the study is that the folks who were in the placebo arm of the original study and did not respond, now have a shot at getting a drug whose initial results against the HCV virus are very positive. One of the problems with experimental studies, particularly early stage studies, is that there is always an arm of the study that does not receive the experimental drug and thus you are potentially both entering a difficult treatment process and giving up your treatment-naïve status and not getting anything but the treatment you would have received outside of the study. Here, even the folks in the placebo arm who did not respond, will get a chance to attack their Hep C with cutting-edge treatment.
The other positive news is that the safety issues they were testing for regarding possible kidney damage have shown themselves to be of lesser importance. One of the reasons they are adding this arm to the study, I was told by my research coordinator, was that the kidney problems were not showing up in the test subjects so far in the study. That is one of the reasons that the length of treatment in the Group F arm will be extended to 24 weeks from the 12 weeks of treatment the rest of the study arms received. The researchers believe they can give the drug for longer periods without undue fear of kidney damage.
There is another potential development in the study as well. There is a petition in front of the study governors to allow test subjects in the low dose arm (Group A) of the study who had rebounds in their HCV Viral Load amounts to join the Group F arm as well. Group A received 500mg of RO5024048 twice a day, the other arms receiving the experimental drug either received higher doses (1000mg twice daily) or a more concentrated dose (1000mg once daily). There is apparently some thought that the dose in Group A might not have been powerful enough to have the desired effect on the virus and that by including those patients in Group F, they would find out if a higher dose had the desired effect even on people who had been already treated with the RO5024048.
The developments in the trial seem all to the positive to me. People who did not respond to the SOC placebo treatment, get a chance to actually receive the experimental triple-drug therapy, the kidney damage issues seem to be less of a concern than originally thought and finally even those who did not respond to a low dose of the drug might get a chance to see if a high dose can smack down their Hep C.
What is happening is that Roche is adding another treatment arm to the study. In this arm “The safety and efficacy of open-label HCV polymerase inhibitor Prodrug (RO5024048) in combination with PEG-INF and RBV in the subset of patients who only received currently approved combination of SOC in the main study and who did not demonstrate an early virologic response (Treatment Failures) will be evaluated.” What this means is that the people in the arm of the study that received the SOC (pegylated interferon and ribavirin) and did not receive the experimental drug and who did not have a log 210 reduction in virus after 12 weeks or who had virus still in the blood after 24 weeks and thus had to stop taking all medications will get a shot at receiving the full triple-drug therapy.
The new arm (Group F) will take RO5024048 1000mg twice daily for 24 weeks in combination with the SOC of weekly Pegasys (interferon) and daily Copegus (ribavirin), followed by an additional 24 weeks of the SOC (Pegasys and Copegus). The study will be open-label meaning patients and doctors will know the medications they are receiving.
The best aspect of this new arm being added to the study is that the folks who were in the placebo arm of the original study and did not respond, now have a shot at getting a drug whose initial results against the HCV virus are very positive. One of the problems with experimental studies, particularly early stage studies, is that there is always an arm of the study that does not receive the experimental drug and thus you are potentially both entering a difficult treatment process and giving up your treatment-naïve status and not getting anything but the treatment you would have received outside of the study. Here, even the folks in the placebo arm who did not respond, will get a chance to attack their Hep C with cutting-edge treatment.
The other positive news is that the safety issues they were testing for regarding possible kidney damage have shown themselves to be of lesser importance. One of the reasons they are adding this arm to the study, I was told by my research coordinator, was that the kidney problems were not showing up in the test subjects so far in the study. That is one of the reasons that the length of treatment in the Group F arm will be extended to 24 weeks from the 12 weeks of treatment the rest of the study arms received. The researchers believe they can give the drug for longer periods without undue fear of kidney damage.
There is another potential development in the study as well. There is a petition in front of the study governors to allow test subjects in the low dose arm (Group A) of the study who had rebounds in their HCV Viral Load amounts to join the Group F arm as well. Group A received 500mg of RO5024048 twice a day, the other arms receiving the experimental drug either received higher doses (1000mg twice daily) or a more concentrated dose (1000mg once daily). There is apparently some thought that the dose in Group A might not have been powerful enough to have the desired effect on the virus and that by including those patients in Group F, they would find out if a higher dose had the desired effect even on people who had been already treated with the RO5024048.
The developments in the trial seem all to the positive to me. People who did not respond to the SOC placebo treatment, get a chance to actually receive the experimental triple-drug therapy, the kidney damage issues seem to be less of a concern than originally thought and finally even those who did not respond to a low dose of the drug might get a chance to see if a high dose can smack down their Hep C.
Monday, March 22, 2010
Ribavirin, You Take My Breath Away.
Friday the 19th I went in for my week 14 tests. I have now been off the RG-7128 aka RO5024048 study meds for two weeks. They took the usual 15 vials of blood. AG, the other study coordinator, told me that one reason she likes Roche studies is that they do a lot of testing for safety. She said they are concerned about certain test results and side effects that some other drug companies view as peripheral. That is some comfort although the constant returns to the lab for retesting and redraws of blood is grinding me down.
The good news is that the Viral Load remains undetectable. It has now been 6 weeks since I went undetectable. This is an excellent result and makes continuing the study easier to do. Having an EVR is a positive sign for obtaining a sustained viral response (SVR) and being declared cleared of the virus (the doctor’s term) or cured of the virus (the drug company’s term).
The bad news is that my hemoglobin is down to 9.9 on their scale. Normal hemoglobin is 12.7 – 17.00, my baseline was 14.8; this means I am now short about 33% or one third of my hemoglobin and boy does it show. I was walking along the waterfront in San Francisco on Sunday with my wife. I was a short walk of about 1 mile round trip. I had to sit down at the halfway point. Even though I know the reason for it, this just drives me crazy. I hate not being able to physically do the things I would normally be able to do easily. Imagine for yourself doing all the things you normally do during a day only doing them with one third less oxygen in your blood. It tends to make you take things quite a bit slower.
I did a Saturday shift at my job a few weeks ago. This involved running a book sale and boxing up the books after the sale. I had some volunteers to help and they did a great job, but I had to do a lot of boxing and lifting. When I got home, I soaked in the tub for an hour or so and went to bed early. While the next day wasn’t bad, the following Monday, I was barely able to stay awake at work and my boss sent me home early because I looked so exhausted it was beginning to depress our (mostly much older than me) volunteers.
All this keeps bringing me back to what I read in one of the Hep C books, “be patient with yourself, you will not have the same capacity you did before starting treatment.” The book has it exactly right. The problem is actually being patient with yourself. If you had any level of energy and drive before starting treatment, the state you find yourself in whilst on treatment will depress the hell out of you.
I had a great conversation about this with my kid sister the other day and she told me to put down the date I will be ending treatment on the calendar, and to plan to celebrate it in some way. She emphasized that it will be over eventually and things will return to normal. Her advice was that prominently noting the date of the end of treatment would reinforce the concept that there is a definite end to the process. I wonder if spray-painting the date across the front of the house might be going too far; maybe a neon sign? Whatever will put the idea firmly in my head that this too will pass is what I want to do.
One last thought comes to mind about all this. There was a closing page article in the latest Liver Health Today about a guy in Texas who is doing very well while on treatment. He is a hemophiliac with HIV and Hep C. He got himself into top shape over the past few years and has been riding in 100-mile bike races. When he started Hep C treatment, he noted that it slowed him down for a few weeks, but that after a few months he was back and the bike and recently rode in a 150-mile race. He attributes his success to being in shape and to his Christianity. I can’t dispute any of this and in fact I applaud him for his dedication and his ability to deal with adversity and challenge. At our support group, the overwhelming feeling was that stories like this are in some ways inspirational but in many other ways depressing. One of our folks did a 72-week stint of treatment and there were times she could barely move around her house, she was so exhausted. Others talked about being thrilled that they could ride a bike for a bit or going to the golf driving range. Not one of all the people I have talked to who have gone through treatment came close to this gentleman’s achievement. So, is it inspirational or is it egotistical to report these sorts of stories. Don’t know, but the vast majority of us are more in the middle of the bell curve and might be able to use a bit encouragement and advice that actually seems possible.
The good news is that the Viral Load remains undetectable. It has now been 6 weeks since I went undetectable. This is an excellent result and makes continuing the study easier to do. Having an EVR is a positive sign for obtaining a sustained viral response (SVR) and being declared cleared of the virus (the doctor’s term) or cured of the virus (the drug company’s term).
The bad news is that my hemoglobin is down to 9.9 on their scale. Normal hemoglobin is 12.7 – 17.00, my baseline was 14.8; this means I am now short about 33% or one third of my hemoglobin and boy does it show. I was walking along the waterfront in San Francisco on Sunday with my wife. I was a short walk of about 1 mile round trip. I had to sit down at the halfway point. Even though I know the reason for it, this just drives me crazy. I hate not being able to physically do the things I would normally be able to do easily. Imagine for yourself doing all the things you normally do during a day only doing them with one third less oxygen in your blood. It tends to make you take things quite a bit slower.
I did a Saturday shift at my job a few weeks ago. This involved running a book sale and boxing up the books after the sale. I had some volunteers to help and they did a great job, but I had to do a lot of boxing and lifting. When I got home, I soaked in the tub for an hour or so and went to bed early. While the next day wasn’t bad, the following Monday, I was barely able to stay awake at work and my boss sent me home early because I looked so exhausted it was beginning to depress our (mostly much older than me) volunteers.
All this keeps bringing me back to what I read in one of the Hep C books, “be patient with yourself, you will not have the same capacity you did before starting treatment.” The book has it exactly right. The problem is actually being patient with yourself. If you had any level of energy and drive before starting treatment, the state you find yourself in whilst on treatment will depress the hell out of you.
I had a great conversation about this with my kid sister the other day and she told me to put down the date I will be ending treatment on the calendar, and to plan to celebrate it in some way. She emphasized that it will be over eventually and things will return to normal. Her advice was that prominently noting the date of the end of treatment would reinforce the concept that there is a definite end to the process. I wonder if spray-painting the date across the front of the house might be going too far; maybe a neon sign? Whatever will put the idea firmly in my head that this too will pass is what I want to do.
One last thought comes to mind about all this. There was a closing page article in the latest Liver Health Today about a guy in Texas who is doing very well while on treatment. He is a hemophiliac with HIV and Hep C. He got himself into top shape over the past few years and has been riding in 100-mile bike races. When he started Hep C treatment, he noted that it slowed him down for a few weeks, but that after a few months he was back and the bike and recently rode in a 150-mile race. He attributes his success to being in shape and to his Christianity. I can’t dispute any of this and in fact I applaud him for his dedication and his ability to deal with adversity and challenge. At our support group, the overwhelming feeling was that stories like this are in some ways inspirational but in many other ways depressing. One of our folks did a 72-week stint of treatment and there were times she could barely move around her house, she was so exhausted. Others talked about being thrilled that they could ride a bike for a bit or going to the golf driving range. Not one of all the people I have talked to who have gone through treatment came close to this gentleman’s achievement. So, is it inspirational or is it egotistical to report these sorts of stories. Don’t know, but the vast majority of us are more in the middle of the bell curve and might be able to use a bit encouragement and advice that actually seems possible.
Thursday, March 4, 2010
Up, Down, All Around
There are ups and downs to this research regimen. Yesterday, I went in for my 12-week tests. I am finishing the experimental drug tomorrow. They needed to determine how fast the drug disseminates into the bloodstream, so the time of the testing was controlled so that they could take blood samples at specific times after I had taken my dose of the meds. None of this is a particularly big deal, it just means a bit more time and a few more questions to answer. It is interesting to note that, despite the attempts to make these tests consistent and rigorous, the human error factor rears its head from time to time. In previous visits, they have forgotten to take my weight, in this test they took my weight, but forgot to take my blood pressure and temperature. I’m sure somebody got a ding for that as they have been quite concerned about the state of my blood pressure throughout the project thus far.
I came in to this visit with a sore throat and told AVB that I had the sore throat, some coughing and nasal stuff. We also discussed the side effects, which ones were decreasing (itching, general cough, irritability) and which were either steady or increasing (fatigue, shortness of breath, muscle weakness). I then went off for the blood draws for this round.
They took 17 vials of blood. The blood guy (who has been drawing my blood for several visits now) estimated that it was from 18-20 ounces of blood. This is roughly the amount that they have been taking since the beginning of the test. So they took about a pint at the start of the test, at weeks one, two, four, eight, ten and twelve or roughly 7 pints of blood in 12 weeks. Despite their claims to the contrary this has to be stressing all my systems. This is a lot of blood to be replacing in normal circumstances, but given that my red cell and white cell producing systems are both being suppressed by the Interferon and Ribavirin as well as some additional white cell suppression by the RO5024048 Polymerase Inhibitor, I can’t believe it is without consequences.
I think I am living them now as the sore throat and developed into a full-blown flu-like outbreak last night and today. Mild fever, productive cough, sore throat, all the delights of flu. Sure I could have developed this anyway, but somehow having over a pint of blood withdrawn just while it was coming on seems like it must have contributed to the onset. Who knows? I did get vaccinated for both strains of flu this year and that has to help, but I think that if the timing of all this were different, I might have a milder case of this. In any case, I’m going to delay my Interferon injection for a day to give my immune system a bit of help before dosing it again with an inhibiting agent.
The good news: Still Undetectable. It is now officially 3 taqman tests showing undetectability. This is great news and I will celebrate accordingly when the flu goes away. Really, I promise.
I came in to this visit with a sore throat and told AVB that I had the sore throat, some coughing and nasal stuff. We also discussed the side effects, which ones were decreasing (itching, general cough, irritability) and which were either steady or increasing (fatigue, shortness of breath, muscle weakness). I then went off for the blood draws for this round.
They took 17 vials of blood. The blood guy (who has been drawing my blood for several visits now) estimated that it was from 18-20 ounces of blood. This is roughly the amount that they have been taking since the beginning of the test. So they took about a pint at the start of the test, at weeks one, two, four, eight, ten and twelve or roughly 7 pints of blood in 12 weeks. Despite their claims to the contrary this has to be stressing all my systems. This is a lot of blood to be replacing in normal circumstances, but given that my red cell and white cell producing systems are both being suppressed by the Interferon and Ribavirin as well as some additional white cell suppression by the RO5024048 Polymerase Inhibitor, I can’t believe it is without consequences.
I think I am living them now as the sore throat and developed into a full-blown flu-like outbreak last night and today. Mild fever, productive cough, sore throat, all the delights of flu. Sure I could have developed this anyway, but somehow having over a pint of blood withdrawn just while it was coming on seems like it must have contributed to the onset. Who knows? I did get vaccinated for both strains of flu this year and that has to help, but I think that if the timing of all this were different, I might have a milder case of this. In any case, I’m going to delay my Interferon injection for a day to give my immune system a bit of help before dosing it again with an inhibiting agent.
The good news: Still Undetectable. It is now officially 3 taqman tests showing undetectability. This is great news and I will celebrate accordingly when the flu goes away. Really, I promise.
Sunday, February 28, 2010
Deciding About Treatment – Lot’s to Think About
I have had several people ask me why I decided to enter treatment. Specifically, they wanted to know why now?
My situation was this: 56 years old, high viral load at 13,000,000 per ml of blood, stage 1 liver disease, my Hep C had been symptomatic for 18-24 months.
Mine was not a desperate situation, no advanced liver disease, symptoms were present and annoying but not yet debilitating, and I was not in poor health generally. It came down to a long and serious consideration of a number of variables from health to work to family considerations. Here are some of the considerations:
What is the stage of your liver disease? Clearly, if you have advanced liver disease, treatment becomes something much more important and possibly mandatory than if your liver is not so deteriorated. If it early stage, you have the gift of time to consider all your options and potentially await additional treatment developments. If it is late stage, you have to decide much more quickly as the consequences of putting off treatment become exponentially more serious.
What is the state of your general health? Is the Hep C directly attacking your health through its symptoms and side effects and/or is the state of your liver creating additional health issues that are threatening or debilitating? To a certain extent the poorer your health, the more difficult the side effects of the treatment may be, but the more important it may well be to begin treatment in order to battle the effects of the disease. Again, the better your general health, the less immediate the decision becomes.
How are the general Hep C symptoms affecting you? Are you able to use available therapies to mitigate the effects of the symptoms of Hep C? Fatigue, Depression and Brain Fog are 3 of the more widely reported symptoms of Hep C. There are also joint pain, Ascites or fluid build-up in the abdomen, weight loss and the really serious symptoms of late-stage liver disease. There are a number of therapies for the general symptoms and if you are using them successfully and your life seems to be stable and at an acceptable level of health, this affects your decision. If the symptoms are beginning to overwhelm you, or become more than is tolerable for you, this also will have a large influence on your choice.
What is your health insurance situation? Hugely important of course. In countries with government financed health care systems this is a bit less of a concern, though the time before you can get authorization and enter treatment has to be considered carefully. If you have private health insurance, does it cover Hep C at all and if so, which of the therapies does it cover and for how long? If you eventually have to change insurers, will your Hep C be considered a per-existing condition and therefore the treatment would not be covered by insurance? Does this mean you should go for it while it is still covered? These are really tough questions and can definitely make the difference in treatment decisions. Something as basic as timing your treatment to begin the year right after your insurance renews can make all the difference in being covered through the entire length of treatment.
What is your employment or general work situation? This is a multifaceted question. If you are self-employed or run your own business, can you keep it going while not being able to put in the 40-60 hours per week that self-employment and business ownership generally require. Do you have people who can pick up the slack and help you during the 48 or more weeks that you will be, most likely, not at your best? Can your company survive if you have to take some time off without being able to work much at all?
If you are employed, what is your employer’s attitude going to be? Can you let anyone know you have Hep C? Is it clear to you that the attitudes at work would not be in your favor if they knew you had the disease? While it is illegal to discriminate against someone with a chronic disease like Hep C, remember that the burden of proof is on you. Should it come down to contesting a lay-off or firing, you have to bring the case and prove the action was because of Hep C.
If you believe that there is support from your employer what form will it take? Can you work a shortened workday or 4 day week? Can you take time off during the day to rest if necessary? Will they be supportive of the time you need to visit doctors and have tests? Do you have a sick leave policy or accumulated sick time that can be used to make up the time that you cannot be at the job? All these questions are vitally important and must be considered carefully before you make choices about treatment.
Which Genotype of the Virus am I and what are the chances for success? The common genotypes in North America are genotypes 1, 2 and 3. Genotype 1 is the most common and conversely, the most difficult to treat successfully. Genotypes 2 &3 are much less common in North America (and much more common in the rest of the world) and have a much higher success rate with treatment. The Standard of Care (SOC) is pegylated interferon (Pegasys, Peg-Intron) and Ribavirin (Copagus) taken for 48 weeks. The percentage of patients with a Sustained Virologic Response (SVR) is about 46% for genotype 1 and 80+% for genotypes 2 &3. So you have a bit less than a 50-50 shot to be cleared of the virus after treatment if you have the most common genotype present in the USA. The question boils down to: do you want to endure the effects of treatment for a year (and then some recovery time as well) for a 50-50 shot at a cure?
This is where the question of experimental drug studies comes into consideration. The study I am in uses a polymerase inhibitor (RO5024048) in addition to the SOC. The early studies indicated that it could result in a SVR rate of upwards of 70% in genotype 1 patients. There are very advanced compounds in the protease inhibitor family (Telaprevir is one example) that have shown in phase 3 studies that they have SVR rates of about 64%. When you see these sorts of results, the question changes quite a bit. Can I deal with treatment for a year if it means I have a 2-1 shot at clearing the virus or even a 3-1 shot?
What is your family situation? How stable is your relationship? How do you think your partner and/or children will react to the situation? Will they support you through the difficult parts of treatment? Does your family have the necessary financial means to deal with the potential loss of income and increased costs brought on by undergoing treatment? These are all highly personal questions whose answers are different for every individual considering treatment. They can also be questions whose answers change over time. Sometimes folks can start out very supportive and be worn down over time. Other times people step up to offer support and assistance in ways that can be astonishing in their generosity.
These are just some of the questions that arise when considering treatment. More to come…
My situation was this: 56 years old, high viral load at 13,000,000 per ml of blood, stage 1 liver disease, my Hep C had been symptomatic for 18-24 months.
Mine was not a desperate situation, no advanced liver disease, symptoms were present and annoying but not yet debilitating, and I was not in poor health generally. It came down to a long and serious consideration of a number of variables from health to work to family considerations. Here are some of the considerations:
What is the stage of your liver disease? Clearly, if you have advanced liver disease, treatment becomes something much more important and possibly mandatory than if your liver is not so deteriorated. If it early stage, you have the gift of time to consider all your options and potentially await additional treatment developments. If it is late stage, you have to decide much more quickly as the consequences of putting off treatment become exponentially more serious.
What is the state of your general health? Is the Hep C directly attacking your health through its symptoms and side effects and/or is the state of your liver creating additional health issues that are threatening or debilitating? To a certain extent the poorer your health, the more difficult the side effects of the treatment may be, but the more important it may well be to begin treatment in order to battle the effects of the disease. Again, the better your general health, the less immediate the decision becomes.
How are the general Hep C symptoms affecting you? Are you able to use available therapies to mitigate the effects of the symptoms of Hep C? Fatigue, Depression and Brain Fog are 3 of the more widely reported symptoms of Hep C. There are also joint pain, Ascites or fluid build-up in the abdomen, weight loss and the really serious symptoms of late-stage liver disease. There are a number of therapies for the general symptoms and if you are using them successfully and your life seems to be stable and at an acceptable level of health, this affects your decision. If the symptoms are beginning to overwhelm you, or become more than is tolerable for you, this also will have a large influence on your choice.
What is your health insurance situation? Hugely important of course. In countries with government financed health care systems this is a bit less of a concern, though the time before you can get authorization and enter treatment has to be considered carefully. If you have private health insurance, does it cover Hep C at all and if so, which of the therapies does it cover and for how long? If you eventually have to change insurers, will your Hep C be considered a per-existing condition and therefore the treatment would not be covered by insurance? Does this mean you should go for it while it is still covered? These are really tough questions and can definitely make the difference in treatment decisions. Something as basic as timing your treatment to begin the year right after your insurance renews can make all the difference in being covered through the entire length of treatment.
What is your employment or general work situation? This is a multifaceted question. If you are self-employed or run your own business, can you keep it going while not being able to put in the 40-60 hours per week that self-employment and business ownership generally require. Do you have people who can pick up the slack and help you during the 48 or more weeks that you will be, most likely, not at your best? Can your company survive if you have to take some time off without being able to work much at all?
If you are employed, what is your employer’s attitude going to be? Can you let anyone know you have Hep C? Is it clear to you that the attitudes at work would not be in your favor if they knew you had the disease? While it is illegal to discriminate against someone with a chronic disease like Hep C, remember that the burden of proof is on you. Should it come down to contesting a lay-off or firing, you have to bring the case and prove the action was because of Hep C.
If you believe that there is support from your employer what form will it take? Can you work a shortened workday or 4 day week? Can you take time off during the day to rest if necessary? Will they be supportive of the time you need to visit doctors and have tests? Do you have a sick leave policy or accumulated sick time that can be used to make up the time that you cannot be at the job? All these questions are vitally important and must be considered carefully before you make choices about treatment.
Which Genotype of the Virus am I and what are the chances for success? The common genotypes in North America are genotypes 1, 2 and 3. Genotype 1 is the most common and conversely, the most difficult to treat successfully. Genotypes 2 &3 are much less common in North America (and much more common in the rest of the world) and have a much higher success rate with treatment. The Standard of Care (SOC) is pegylated interferon (Pegasys, Peg-Intron) and Ribavirin (Copagus) taken for 48 weeks. The percentage of patients with a Sustained Virologic Response (SVR) is about 46% for genotype 1 and 80+% for genotypes 2 &3. So you have a bit less than a 50-50 shot to be cleared of the virus after treatment if you have the most common genotype present in the USA. The question boils down to: do you want to endure the effects of treatment for a year (and then some recovery time as well) for a 50-50 shot at a cure?
This is where the question of experimental drug studies comes into consideration. The study I am in uses a polymerase inhibitor (RO5024048) in addition to the SOC. The early studies indicated that it could result in a SVR rate of upwards of 70% in genotype 1 patients. There are very advanced compounds in the protease inhibitor family (Telaprevir is one example) that have shown in phase 3 studies that they have SVR rates of about 64%. When you see these sorts of results, the question changes quite a bit. Can I deal with treatment for a year if it means I have a 2-1 shot at clearing the virus or even a 3-1 shot?
What is your family situation? How stable is your relationship? How do you think your partner and/or children will react to the situation? Will they support you through the difficult parts of treatment? Does your family have the necessary financial means to deal with the potential loss of income and increased costs brought on by undergoing treatment? These are all highly personal questions whose answers are different for every individual considering treatment. They can also be questions whose answers change over time. Sometimes folks can start out very supportive and be worn down over time. Other times people step up to offer support and assistance in ways that can be astonishing in their generosity.
These are just some of the questions that arise when considering treatment. More to come…
Monday, February 22, 2010
On the Road Again – Yet Another Retest
My lymphocytes are low again and they brought me in for another retest. They are at 410 and anything under 500 warrants a retest as they are being conservative for the purposes of the study. AVB told me that in standard clinical practice the lymphocytes can drop to 350 before they take action. I wish that were the case as this seemingly constant traipsing back and forth for a couple of vials of blood is tiresome.
I realize the complaint is a hollow one. I am, after all, getting a cutting edge and, to this point, extremely effective new compound to attack my Hep C. But after 11 weeks now of being tired and breathless and fogged in the head, it just starts to get less exciting. Even the fact that a whole new set of health care professionals know me by name begins to lose its charm.
The good news is they gave me my latest (week 10) viral load results and I am still UNDECTECTABLE. 3 straight tests covering 4 weeks of time at that level. Keep it up guys, look under every molecule to find those viruses and kill them. There is no peaceful coexistence with this virus. I want them all dead, even to the bits and pieces. There is some small mental exhilaration in having something I can root wholeheartedly to be destroyed, killed, eradicated and just stomped on. Free your inner barbarian and have it join with the RG-7128 aka RO5024048 and just go out and slaughter.
I realize the complaint is a hollow one. I am, after all, getting a cutting edge and, to this point, extremely effective new compound to attack my Hep C. But after 11 weeks now of being tired and breathless and fogged in the head, it just starts to get less exciting. Even the fact that a whole new set of health care professionals know me by name begins to lose its charm.
The good news is they gave me my latest (week 10) viral load results and I am still UNDECTECTABLE. 3 straight tests covering 4 weeks of time at that level. Keep it up guys, look under every molecule to find those viruses and kill them. There is no peaceful coexistence with this virus. I want them all dead, even to the bits and pieces. There is some small mental exhilaration in having something I can root wholeheartedly to be destroyed, killed, eradicated and just stomped on. Free your inner barbarian and have it join with the RG-7128 aka RO5024048 and just go out and slaughter.
Wednesday, February 17, 2010
Week 10 Tests and Week 8 Results
Today was week 10 testing. All the usual tests though only 11 vials of blood for this series.
The important point to me was the Week 8 test results: viral load UNDECTECTABLE. Unlike week 6 when the test detected viral activity though the number of virus per ml was so low as to be uncountable, this time the test reported no detectable viral activity at all. So there it is, the polymerase inhibitor RG-7128 aka RO5024048 knocked the virus down from just under 13 million per ml to undetectable in 8 weeks.
AVB told me that the earlier a patient achieved the undetectable level, the better the chances are for an SVR (sustained viral response) over the long term. Eight weeks is pretty fast in general and tremendous for someone with my initial viral load. A few of the folks I have talked to about there treatment told me that they started with what was considered a high viral load and theirs was in the 3 to 4 million per ml range. Mine was about 4 times that number at the start of the treatment.
While it does not seem to have added any significant side effects to the general run of the SOC side effects, it doesn’t seem to have reduced any of them either.
The other good news was that my neutrophil count had bounced back up over the 500 level and I could continue the experimental drug. Even though I have hit undetectable levels and there is only 2 weeks left in the polymerase inhibitor part of the experiment, I still want to have the full course of treatment. I want that extra two weeks of this drug completely screwing up the ability of any virus left to reproduce. I want the full amount of destruction to be visited upon this virus. I want them hunted down and killed for as long as possible by the most complete range of attack drugs.
The main new factor to report on the side effect front is that my concentration and memory are continuing to deteriorate. As an example, I did not bring in a chilled urine sample for this test period. Why not, you ask. Because I stepped in to the bathroom after I woke up with my urine collection cup in hand, set it down on the sink and then urinated luxuriously and at length while completely forgetting to get a sample of if for the test. I remembered my test appointment and brought all my stuff with me, but remembering to piss in a cup was more than my brain was capable of.
The important point to me was the Week 8 test results: viral load UNDECTECTABLE. Unlike week 6 when the test detected viral activity though the number of virus per ml was so low as to be uncountable, this time the test reported no detectable viral activity at all. So there it is, the polymerase inhibitor RG-7128 aka RO5024048 knocked the virus down from just under 13 million per ml to undetectable in 8 weeks.
AVB told me that the earlier a patient achieved the undetectable level, the better the chances are for an SVR (sustained viral response) over the long term. Eight weeks is pretty fast in general and tremendous for someone with my initial viral load. A few of the folks I have talked to about there treatment told me that they started with what was considered a high viral load and theirs was in the 3 to 4 million per ml range. Mine was about 4 times that number at the start of the treatment.
While it does not seem to have added any significant side effects to the general run of the SOC side effects, it doesn’t seem to have reduced any of them either.
The other good news was that my neutrophil count had bounced back up over the 500 level and I could continue the experimental drug. Even though I have hit undetectable levels and there is only 2 weeks left in the polymerase inhibitor part of the experiment, I still want to have the full course of treatment. I want that extra two weeks of this drug completely screwing up the ability of any virus left to reproduce. I want the full amount of destruction to be visited upon this virus. I want them hunted down and killed for as long as possible by the most complete range of attack drugs.
The main new factor to report on the side effect front is that my concentration and memory are continuing to deteriorate. As an example, I did not bring in a chilled urine sample for this test period. Why not, you ask. Because I stepped in to the bathroom after I woke up with my urine collection cup in hand, set it down on the sink and then urinated luxuriously and at length while completely forgetting to get a sample of if for the test. I remembered my test appointment and brought all my stuff with me, but remembering to piss in a cup was more than my brain was capable of.
Friday, February 12, 2010
Testing, Testing, Testing
I went in today for a retest of my Neutrophil count. This endless testing is beginning to wear. Since the start of the Study, I have been in for Baseline testing and week 2,4,6 and 8 testing each of which involved drawing 10-16 vial of blood. I have also been called back for retests my Neutrophil and Hemogloblin levels after the last 3 tests. I have been to visit these guys 8 times in 9 weeks for various testing.
I am extremely lucky that I live in San Francisco. At least one of the test subjects lives in Eureka, which is a good 5-6 hour drive from the Bay Area. I can only hope they have not had to have any retesting, or if they have, that Roche has contracted with a lab in that general area to do the retests. If I had to drive 5 hours to have them draw 2 vials of blood to verify a borderline result, it would piss me off no end.
I know that they are doing this because the fact that they are testing an experimental drug makes them extremely cautious. The various levels that are causing them concern are levels above those they accept during standard treatment. One of the individuals in our support group had their Hemoglobin drop into the low 9’s during their treatment. In my case if it drops below 10 (and it has been testing that borderline for a few weeks now) they will reduce my Ribavirin dosage to try to forestall any further drop in the level.
There attention and care are appreciated but it feels like the Hepatology Dept. of California Pacific Medical Center is becoming a second home and while everyone is very supportive, positive and friendly, there are better places to be than in a waiting room, an examination room or a blood drawing site.
And just to make sure that I don’t present myself as not being self-serving – we don’t get paid for the retesting visits only for the scheduled testing visits. It’s not the money per se, but it is the fact that even for someone as conveniently located as myself, any visit requires a minimum of 2 hours time and generally 3 for the long visits. You have to get there, be there and get back home or to work and all that takes time and energy. But, hey I’m not going to go on strike and the experiment is working, at least on me.
The major worry is that if the low levels of Neutrophils are confirmed, they will remove me from the experimental drug, the RO5024048 aka RG7128. That’s the stuff that has been working and it is definitely the stuff I want to continue. Go ahead and reduce the Interferon or Ribavirin dose, just don’t take away my Attila the Hun drug. I want to have those ruthless little molecules hunting and killing virus for as long as I possibly can.
It boils down to spending a couple of hours having 2 vials of blood taken so they can recheck blood component levels to determine whether or not I get to keep getting “the good stuff” as long as I possibly can.
No pressure in that eh?
I am extremely lucky that I live in San Francisco. At least one of the test subjects lives in Eureka, which is a good 5-6 hour drive from the Bay Area. I can only hope they have not had to have any retesting, or if they have, that Roche has contracted with a lab in that general area to do the retests. If I had to drive 5 hours to have them draw 2 vials of blood to verify a borderline result, it would piss me off no end.
I know that they are doing this because the fact that they are testing an experimental drug makes them extremely cautious. The various levels that are causing them concern are levels above those they accept during standard treatment. One of the individuals in our support group had their Hemoglobin drop into the low 9’s during their treatment. In my case if it drops below 10 (and it has been testing that borderline for a few weeks now) they will reduce my Ribavirin dosage to try to forestall any further drop in the level.
There attention and care are appreciated but it feels like the Hepatology Dept. of California Pacific Medical Center is becoming a second home and while everyone is very supportive, positive and friendly, there are better places to be than in a waiting room, an examination room or a blood drawing site.
And just to make sure that I don’t present myself as not being self-serving – we don’t get paid for the retesting visits only for the scheduled testing visits. It’s not the money per se, but it is the fact that even for someone as conveniently located as myself, any visit requires a minimum of 2 hours time and generally 3 for the long visits. You have to get there, be there and get back home or to work and all that takes time and energy. But, hey I’m not going to go on strike and the experiment is working, at least on me.
The major worry is that if the low levels of Neutrophils are confirmed, they will remove me from the experimental drug, the RO5024048 aka RG7128. That’s the stuff that has been working and it is definitely the stuff I want to continue. Go ahead and reduce the Interferon or Ribavirin dose, just don’t take away my Attila the Hun drug. I want to have those ruthless little molecules hunting and killing virus for as long as I possibly can.
It boils down to spending a couple of hours having 2 vials of blood taken so they can recheck blood component levels to determine whether or not I get to keep getting “the good stuff” as long as I possibly can.
No pressure in that eh?
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