[Phase I clinical study of CPT-11. Research group of CPT-11].
CPT-11 is a new derivative of Camptothecin. Phase I clinical study of single administration with CPT-11 was carried out by a cooperative study group. Starting from 50 mg/m2 (n), dose was escalated to 350 mg/m2 (7n). Dose limiting factor was found to be a decrease in WBC counts (especially in neutrophils), and MTD was presumed to be 250 mg/m2 or more. Nadir of WBC counts was observed after about a week, and it took 2-3 weeks for recovery. The decrease in platelet number and hemoglobin content was mild. Other side effects included G-I toxicities, alopecia, etc. However, no toxic effects on the heart, kidney, lung were observed. SN-38, main metabolite of CPT-11, was observed in blood, and excreted rapidly. Anticancer effects were suggested with dose of 165 mg/m2 or more against colon cancer, gastric sarcoma, melanoma and lung cancer. It is suggested that the optimal dose schedule for an early Phase II study is 200 mg/m2 every 3-4 weeks. However, not only leukopenia but also marked G-I toxicities being noted in some cases, care should be taken for those side effects.
Dept. of Surgery, Research Inst. for Microbial Diseases, Osaka University.
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T
Taguchi
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Wakui
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Hasegawa
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Niitani
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Furue
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Ohta
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Hattori
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004341:Drug Evaluation; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy; D006801:Humans; D000077146:Irinotecan; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009369:Neoplasms / Q000188:drug therapy*
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin