A phase I study of amrubicin and carboplatin for previously untreated patients with extensive-disease small cell lung cancer.

BACKGROUND: Amrubicin and cisplatin are active in the treatment of small cell lung cancer (SCLC), and carboplatin is an analogue of cisplatin with less nonhematological toxicity. The appropriate dose of amrubicin and carboplatin combination chemotherapy for previously untreated patients with extensive-disease (ED) SCLC has not been established.

PURPOSE: To determine the maximum-tolerated dose and dose-limiting toxicity (DLT) of amrubicin and carboplatin in ED-SCLC.

PATIENTS AND METHODS: Eligibility criteria were chemotherapy-naive ED-SCLC patients, performance status 0-1, age < or =75, and adequate hematological, hepatic, and renal function. Patients received escalating amrubicin doses under a fixed target area under the curve (AUC) 5 of carboplatin (Chatelut formula). Amrubicin and carboplatin were administered by intravenous (IV) infusion on days 1, 2, and 3, and day 1, respectively. The initial dose of amrubicin was 30 mg/m(2), and the dose was escalated to 35 and 40 mg/m(2).

RESULTS: Sixteen patients were enrolled and 15 eligible patients were evaluated. One of six patients in level 1, one of six in level 2, and three of three in level 3 experienced DLTs. The presentation of DLTs included neutropenia, leukopenia, thrombocytopenia, febrile neutropenia, and liver dysfunction. Evaluation of responses were two complete response, nine partial response, three stable disease, and one progressive disease (response rate 73%), and the median survival time was 13.6 months. The maximum-tolerated doses of amrubicin and carboplatin were determined as 40 mg/m(2) and AUC 5. A dose of 35 mg/m(2) amrubicin and carboplatin AUC 5 was recommended in this regimen.

CONCLUSIONS: This regimen is associated with an acceptable tolerability profile, and warrants evaluation in the phase II setting.