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Phase I clinical and pharmacological studies of 20-(S)-camptothecin and 20-(S)-9-nitrocamptothecin as anticancer
E A Natelson1, B C Giovanella, C F Verschraegen
1Stehlin Foundation for Cancer Research, St. Joseph Hospital, Houston, Texas 77003, USA.
Abstract:
Groups of 52 and 29 patients with refractory cancers received either native camptothecin (CPT) or 9-nitrocamptothecin (9NC), respectively, in Phase I clinical trials designed to determine the maximum tolerated dose, toxicity and potential efficacy of orally administered camptothecins. Favorable responses occurred with both compounds (11% after CPT, 24% after 9NC). Although both agents could be taken safely for extended periods, dose limiting toxicities were substantial. Diarrhea was the major clinical problem with CPT, and myelosuppression with 9NC. Both compounds could cause hemorrhagic cystitis. The antitumor activity demonstrated suggests that further investigation of orally administered camptothecin analogs is warranted.