Phase I Study of a Weekly Infusion of Irinotecan Hydrochloride (CPT-11) and a 14-day Continuous Infusion of Etoposide in Patients with Lung Cancer: Japan Clinical Oncology Group 9408

Abstract

Background: To determine the maximum-tolerated dose (MTD) and acceptable dose level of CPT-11 in combination with a 14-day continuous infusion of etoposide in patients with refractory advanced lung cancer (LC), especially small cell lung cancer (SCLC). Methods: Etoposide was administered continuously at 25 mg/m2/day for 14 days. The initial dose of CPT-11 was 40 mg/m2 given as a 90-min intravenous infusion on days 1, 8 and 15 and the dose escalation of CPT-11 was planned in increments of 20 mg/m2 until severe or life-threatening toxic effects were observed. Results: Eight refractory advanced LC patients entered this study, of whom two were not assessable for toxicity because of patient’s refusal and progressive disease. One treatment-related death due to pulmonary toxicity and one patient with hypotension who needed catechol­amine for more than 48 h were observed at a CPT-11 dose of 40 mg/m2. The MTD of CPT-11 was 40 mg/m2. Therapeutic efficacy could be assessed in six patients, of whom two achieved a partial response. Conclusions: This regimen was too toxic and the recommended dose was outside this study. One has to consider pulmonary toxicity when using CPT-11, especially for patients previously treated with cytotoxic agents for which pulmonary toxicity has been reported.