Alert Number 280
Date: March 4, 2008
In one of my recent posts on Harvey's Journal - Planning For Success I quoted a table from a recent M. D. Anderson paper on the response statistics of FCR combination in previously treated patients. In the breakout of patients into sub-categories based on their prior therapy exposure, there were 7 patients that had been exposed to Rituxan therapy and nothing else. 29% of these “Rituxan-virgins” got a CR, a far cry from the much higher percentage of CRs we saw in truly naïve patients who had not been treated with anything.
This statistic drew a lot of attention and caused concern to some patients. Sorry to say, it does not surprise me with my somewhat dour attitude about life - there are no really free lunches out there. But it is a valid point that the sample size of this sub-group was small, only 7 patients. So, to get a more authoritative perspective on Rituxan therapy and impact on subsequent therapy options, I went straight to the source, one of the authors of the paper. Bill Wierda is a scholar and a gentleman. Our email correspondence on the subject is attached below (with his permission).
Bill puts it succinctly. Cancer cells too obey the law of the jungle, survival of the fittest. Nibbling at the edges with Rituxan is likely to kill the cells that are the easiest to kill, leaving behind the tougher customers to grow and increase their eco niche. Any treatment impacts the efficiency of the ones to follow. The logic is hard to ignore.
I hope you will be kind enough to answer a quick question regarding a table in your JCO article on the response statistics of previously treated patients with FCR.
The question is with reference to patients who have only had Rituxan single agent maintenance therapy. Your sample size of this group was small, only 7 patients. But it seems clear from the data that prior exposure to any therapy (even single agent R therapy) has an effect on FCR response statistics, compared to truly naïve patients who have not been treated in any way. It seems quite logical to me that given the high degree of importance of synergy between R and FC parts of the equation, prior exposure to R would have an impact.
Do you agree that even Rituxan only prior therapy still has an impact on subsequent FCR therapy, and these guys are no longer “chemo-naïve” in the full sense of that term?
Thanks for your time.
My impression has been that exposure to any treatment affects response to subsequent treatment, Rituximab (single-agent) is no exception. This also holds for fludarabine, Campath, chlorambucil, combinations, etc. As far as the leukemia cells go, it is survival of the fittest and any exposure to treatment selects for the fit. People try rationalize that Rituximab (single-agent) in previously untreated patients has no significant toxicity. They also think / assume they are not compromising the potential response to subsequent treatment by first receiving single-agent Rituximab, but this is probably not the case based on our limited numbers of patients treated for salvage with FCR.
The first treatment is the best opportunity to achieve a complete remission, getting rid of the largest number of leukemia cells, including the fit. We (I) feel that complete remission is a critically important first objective for treatment in the majority of patients and would recommend a regimen with highest likelihood of achieving this which in our experience has been FCR.
You may use the above quote.
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