A phase II study of dose-intensified weekly concomitant administration of cisplatin and irinotecan in chemonaive patients with extensive-disease small-cell lung cancer.

Irinotecan/cisplatin (IP) is an active regimen for extensive-disease small-cell lung cancer (ED-SCLC). However, the optimal dose/schedule is unsettled. To evaluate the efficacy and safety of a dose-intensified, weekly concomitant administration of IP, we conducted a phase II study in chemo-naive patients with ED-SCLC. Between October 2001 and February 2004, 37 patients were enrolled. Twenty-nine (78%) were male, 21 (57%) had ECOG PS 0 or 1, and the median age was 62 yr. The initial six patients received cisplatin 50 mg/m2 followed by irinotecan 90 mg/m2 iv on d 1 and 8 of a 21-d cycle (dose level I), with one treatment-related death, three febrile neutropenias. Thereafter, the doses of cisplatin and irinotecan were reduced to 40 mg/m2 and 80 mg/m2, respectively (dose level II). The treatment was continued for up to six cycles. The overall response rate was 97%, with a complete response (CR) rate of 26%. The median duration of response was 6.4 mo (range, 1.6-13.1 mo). At a median follow-up of 27.3 mo, the median survival time was 11.1 mo and 1- and 2-yr survival rates were 44.1% and 11.8%, respectively. The median progression-free survival (PFS) was 6.0 mo (range, 1.5-13.1 mo) and 1-year PFS rate was 7%. Major grade 3 or 4 toxicities included neutropenia (89%), anemia (59%), and diarrhea (27%). Despite of significant myelosuppresion, this dose-intensified weekly concomitant administration of cisplatin and irinotecan was feasible. This dose-schedule showed promising activity with high rate of complete remission in patients with ED-SCLC.