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

From December 1994 to July 1997, we conducted a dose escalation study of ir inotecan combined with carboplatin in 17 patients with advanced nonsmall-ce ll 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 concentra tion-time curve dose of 5 mg/ml.min (calculated using Calvert's formula) on day 1. The starting dose of irinotecan was 30 mg/m(2) and dose escalation was done in 10-mg/m(2) increments. Treatment was repeated at 28-day interva ls for at least two cycles. The dose-limiting toxicities were neutropenia a nd thrombocytopenia, since three out of five patients given 60 mg/m(2) of i rinotecan developed grade 4 neutropenia and thrombocytopenia. The overall r esponse rate was 35.3%. The median survival time and the 1-year survival ra te were 10.5 months and 35.3%, respectively. The maximum tolerated dose of irinotecan with this regimen was 60 mg/m(2), while 50 mg/m(2) can be recomm ended for future use. Further studies of this combination in advanced NSCLC are warranted.