Fractionated administration of irinotecan and cisplatin for treatment of lung cancer: a phase I study

A combination chemotherapy of irinotecan (CPT-11) and cisplatin (CDDP) has been reported to be active for lung cancer. In the previous trial, however, diarrhoea and leucopenia became the major obstacle for sufficient dose esc alation of CPT-II to improve the treatment outcome. We conducted a phase I study to investigate whether the fractionated administration of CDDP and CP T-11 at escalated dose was feasible and could improve the treatment outcome . Twenty-four previously untreated patients with unresectable non-small-cel l lung cancer (NSCLC) or extensive disease or small-cell lung cancer (SCLC) were eligible. Both CDDP and CPT-11 were given on days 1 and 8, and repeat ed every 4 weeks. The dose of CDDP was fixed at 60 mg m(-2) and given by l- h infusion before CPT-11 administration. The starting dose of CPT-11 was 40 mg m(-2), and the dose was escalated by an increase of 10 mg m(-2). The ma ximally tolerated dose of CPT-II was determined as 60 mg m(-2) because grad e 4 haematological or grade 3 or 4 non-haematological toxicities developed in six patients out of 11 patients evaluated. Diarrhoea became a dose-limit ing toxicity. The objective response rates were 76% for NSCLC and 1:100% fo r SCLC. The recommended dose of CPT-11 and CDDP in a phase II study will be 50 mg m(-2) and 60 mg m(-2) respectively.