BACKGROUND We conducted a phase I dose escalation study to evaluate the feasibility, maximum tolerated dose (MTD), and recommended dose (RD) of weekly irinotecan combined with fixed-dose carboplatin for patients with untreated small-cell lung cancer (SCLC). METHODS Fifteen patients with chemotherapy-naïve SCLC less than 75 years old were enrolled from 3 institutions. Patients received irinotecan (50-80mg/m(2) on days 1 and 8) and carboplatin (area under the curve, 5.0 on day 1) every 3 weeks, with 3-6 patients treated at each irinotecan dosage level (levels I-IV). The MTD was defined as the dose at which 33% of patients experienced dose-limiting toxicity. RESULTS Eleven patients had a performance status of 1, and 7 patients were more than 70 years old. All but 1 patient were diagnosed with extensive disease. In total, 2 of 3 patients enrolled at level IV (80mg/m(2)) experienced grade 3 diarrhea. Therefore, the MTD was defined as the level IV dose, and the RD was defined as the level III dose (70mg/m(2)). Grade 3 or 4 neutropenia was observed in 60% of patients, and febrile neutropenia was observed in 13% of patients. Four patients experienced grade 3 or 4 anemia, and 6 patients experienced grade 3 or 4 thrombocytopenia. The most common non-hematological adverse events were nausea/vomiting, diarrhea, hypokalemia, and hyponatremia. CONCLUSIONS The MTD of weekly irinotecan was 80mg/m(2), resulting in an RD of 70mg/m(2) for phase II trials.