ANALYSIS OF CUMULATIVE PROBABILITIES SHOWS THAT THE EFFICACY OF 5HT(3) ANTAGONIST PROPHYLAXIS IS NOT MAINTAINED

Purpose: Several investigators have reported that the efficacy of 5HT( 3) receptor antagonists is maintained over repeated cycles of chemothe rapy. These investigators presented conditional probabilities of prote ction. Because conditional analyses by definition only include patient s with protection in previous cycles, the results are flattered. Patie nts and Methods: We applied a novel statistical approach to investigat e whether the efficacy of the 5HT(3) receptor antagonist ICS 205-930 ( tropiseltron) is maintained over repeated cycles of weekly high-dose c isplatin. Overall protection was determined based on cumulative probab ilities with the Kaplan-Meier method. Complete protection was calculat ed with a three state model for transitional probabilities. Eighty-thr ee patients were studied. Results: Over six consecutive cycles, protec tion against both acute and delayed emesis decreased significantly. Th e initial complete and overall protection rates against acute emesis o f 71% and 95%, respectively, decreased to 43% and 72% in the sixth cyc le of chemotherapy, Similarly, the protection rates of 31% and 68% aga inst delayed emesis decreased to 6% and 40%, respectively. Conclusion: We conclude that overall and complete long-term protection is more ac curately measured by cumulative probabilities than with a method that is based on conditional probabilities. Our statistical approach shows that the efficacy of 5HT(3) antagonists is not maintained. (C) 1996 by American Society of Clinical Oncology.