Dose escalation study of irinotecan combined with carboplatin for advanced non-small-cell lung cancer

• Published in: Cancer chemotherapy and pharmacology 2001-08, Vol.48 (2), p.104-108
• Main Authors: TAKEDA, Koji, NEGORO, Shunichi, TAKIFUJI, Nobuhide, NITTA, Takashi, YOSHIMURA, Naruo, TERAKAWA, Kazuhiko, FUKUOKA, Masahiro
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Camptothecin - administration & dosage; Camptothecin - adverse effects; Camptothecin - analogs & derivatives; Carboplatin - administration & dosage; Carboplatin - adverse effects; Carcinoma, Non-Small-Cell Lung - drug therapy; Chemotherapy; Dose-Response Relationship, Drug; Female; Hematologic Diseases - chemically induced; Humans; Irinotecan; Lung Neoplasms - drug therapy; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s002800100316

From December 1994 to July 1997, we conducted a dose escalation study of irinotecan combined with carboplatin in 17 patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum tolerated dose and the dose-limiting toxicities. Irinotecan was administered intravenously over 90 min on days 1, 8 and 15, with carboplatin given at an area under the concentration-time curve dose of 5 mg/ml x min (calculated using Calvert's formula) on day 1. The starting dose of irinotecan was 30 mg/m2 and dose escalation was done in 10-mg/m2 increments. Treatment was repeated at 28-day intervals for at least two cycles. The dose-limiting toxicities were neutropenia and thrombocytopenia, since three out of five patients given 60 mg/m2 of irinotecan developed grade 4 neutropenia and thrombocytopenia. The overall response rate was 35.3%. The median survival time and the 1-year survival rate were 10.5 months and 35.3%, respectively. The maximum tolerated dose of irinotecan with this regimen was 60 mg/m2, while 50 mg/m2 can be recommended for future use. Further studies of this combination in advanced NSCLC are warranted.