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Editor's Note: Peter Rowbotham attended the 2001 meeting of the American Society of Hematology, held from Dec. 7-11 in Orlando, Florida, U.S.A. Rowbotham, whose wife has CML, has long dedicated himself to researching new treatment advances and passing that information along to others. Here, his series is presented verbatim.
By Peter Rowbotham
[Note from Peter: This report, and any following reports, are based on written notes which may be inaccurate or incomplete. Patients should check with medical professionals as necessary.]
[Correction: In the Orlando II report, I referred to Kantarjian's 'surprise' at the decision in a case study. On reviewing my notes, I see that I erred in giving the wrong case study. That is a good warning to be wary of unintended errors in these reports. The actual case was a 50 year old male patient with an HLA matched 52 year old brother. When asked what therapy they would recommend the audience responded electronically as follows: Gleevec 48%; Allogeneic SCT 38%; IFN 13%; Hydrea 1%. What seemed to bother Kantarjian was the 13 % who would opt for IFN instead of Gleevec.]
Listening to many presentations, and looking at lots of slides with graphs and diagrams of cells, their inner workings, and the communication pathways between proteins, serves to score an indelible impression of the most extraordinary complexity at the molecular level. Because of this there is great danger when reporting the findings of oversimplifying what is going on. Even the best researchers are fumbling around in the dark somewhat, in trying to understanding what is happening. Nevertheless, it is the scientific approach, which is yielding ever promising results, and should give us all hope for the future. I think that is what one chairman meant when he quoted Groucho Marx: "Who are you going to believe, me or your own eyes [i.e. the evidence]?" and when another participant quoted Sir Francis Bacon's paradoxical statement: "To be commanded, nature has to be obeyed."
Today there were a lot of papers on the problem of resistance to Gleevec (which means something like, the drug stops working). This seems to be a fact of life, unfortunately, although it is not at all clear how this resistance will play out with Gleevec treatment. There is some good news; the researchers are very excercised with this problem, and there is a lot of work being done. We can hope that solutions to this potential difficulty will be found. It could also be good news that one form of resistance, gene amplification, may be overcome with higher doses, and perhaps even by interrupting therapy for a sufficient period. The other big area of potential resistance is mutations in the kinase domain (without going into a lengthy explanation, this is one site where a number of mutations have been seen). There are other possibilities, and the research to identify and target these is ongoing. It is useful to keep all this in context. There is considerable durability in the chronic phase responses to Gleevec, which is encouraging. If Kantarjian is right, survival times should increase substantially, which will give patients the chance to benefit from new developments.
One way to deal with this potential concern, is to use a combination therapy. There may be more on this tomorrow, but so far nothing obvious has emerged. There are several new agents such as PP1, CGP76030, L-744,832 [a Merck FTI], and the Schering FTI, SCH66336, continues to look interesting (although the results that I saw from the Janssen FTI, R115777, were disappointing). Arsenic Trioxide has also been mentioned positively several times, and that might turn out to be really useful in combination with Gleevec. This whole question of combination therapy is clearly a very important one if most of us are to defeat CML. There is, however, not enough data or research as yet to give us a clear direction. I anticipate that this sense of direction will emerge more clearly over the next year or so.
If we are to reduce the chance of resistance developing through cellular mutations, one strategy might be to live as healthy a life-style as possible. It may not have a major impact, but we should seize whatever weapon is available to us in this battle. So I looked particularly at the Ascorbic Acid (Vitamin C) paper that I previously referred to. According to this Japanese research group, Ascorbic Acid in combination with Gleevec, restored "sensitivity to STI571 in a resistant CML cell line." In other words, it overcame resistance in that particular type of cell in a laboratory situation. As they put it, Ascorbic Acid "might be one of the most useful reagents to overcome the resistance to STI571." I personally don't place too much faith in this, being a natural sceptic, but I've got to admit the graphs were impressive.
My apologies for discussing the resistance problem and the potential for relapses, but it is better that we stand tall and face these real problems than bury our heads in the sand.
p
There are some very important papers tomorrow, and Dr. Druker will receive his prize at the Presidential Symposium. I will write more when I get back to Vancouver and have caught up on sleep.
My regards to all.
Source: Peter Rowbotham, reprinted with permission
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