[Taxotere (docetaxel) and CPT 11 (irinotecan): phase I trials].
Two new drugs from two new chemotherapy compound families were developed concomitantly: Taxoter (docetaxel), a taxane derivate and CPT 11 (irinotecan) a topoisomerase inhibitor. Six phase I trials of Taxoter were performed. The limiting toxicity is neutropenia. The recommended dosage for phase II trial is 100 mg/m2 administered in 1 hour perfusion, every 21 days. Neutropenic fever is unfrequent. Other toxicities are mucositis, skin toxicity, hypersensibility reaction, weight gain and oedema. None of these toxicities were limiting. Six phase I studies were conducted to determine the maximum tolerated dose of CPT 11 (irinotecan). Two different schedules were studied: the weekly 30-90 minutes infusion and an infusion administered every three weeks in one day or daily over three or five consecutive days. The limiting toxicity of the weekly schedule is diarrhea. Therefore the recommended dosage is 100-150 mg/m2/week. While dose limiting toxicities in the three week schedule are diarrhea as well as neutropenia. The recommended dose is 350 mg/m2. Since diarrhea appeared to be the major problem in achieving high dose intensity with CPT 11, a dose escalation trial with drug support against diarrhea was performed. A recommended dosage of 500 mg/m2 is therefore described. These two drugs are under evaluation in a large spectrum of tumors. Their original mechanism of action suggests interesting therapeutic properties. Clinical studies in combination with other drugs are in progress to define the role of topoisomerase I inhibitors and taxane in cancer therapy.
Couteau
C
C
Institut Gustave-Roussy, la Grange, France.
Yakendji
K
K
Terret
C
C
Goncalves
E
E
Armand
J P
JP
D000930:Antidiarrheals / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008139:Loperamide / Q000627:therapeutic use; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy; D017239:Paclitaxel / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D012074:Remission Induction; D043823:Taxoids; D059004:Topoisomerase I Inhibitors
D000930:Antidiarrheals; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D059004:Topoisomerase I Inhibitors; D000077143:Docetaxel; D008139:Loperamide; D000077146:Irinotecan; D017239:Paclitaxel; D002166:Camptothecin
Taxotère (docétaxel) et CPT 11 (irinotecan): les phases I.