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: JCOG trial 9408

Background: The aim was to determine the maximum tolerated dose (MTD) and recommended dose of irinotecan hydrochloride (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/m(2)/day for 14 days. The initial dose of CPT-11 was 40 mg/m(2) 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/m(2) until severe or life-threatening toxic effects were observed. Results: Nine refractory or advanced LC patients (eight at level 1, one at level 2) were entered in this study, of whom two at level 1 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 level 1, a CPT-11 dose of 40 mg/m(2). The MTD of CPT-11 was 40 mg/m(2). Therapeutic efficacy could be assessed in seven patients, of whom two achieved a partial response. Conclusions: This regimen was too toxic and the recommended dose was outside the levels in 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.