A phase I study of amrubicin combined with carboplatin for elderly patients with small-cell lung cancer.

BACKGROUND: Amrubicin, a new anthracycline agent, has shown high activity for small-cell lung cancer (SCLC) with acceptable toxicities in previous studies. However, a combination regimen of platinum and amrubicin for elderly patients has not been reported. In this phase I study, the dose-limiting toxicity (DLT), the maximal tolerable dose (MTD), and the antitumor activity of a combination of amrubicin and carboplatin in elderly patients with SCLC were evaluated.

PATIENTS AND METHODS: Previously untreated elderly patients (> or =70 years old) with SCLC were enrolled in this study. Amrubicin was administered from day 1 to day 3, and carboplatin was administered on day 1 intravenously. The treatment was repeated every 3 weeks. Three escalating dose levels of amrubicin (mg/m)/carboplatin (area under the curve; AUC) (40/4.0, 40/5.0, and 45/5.0) were initially planned.

RESULTS: Twelve patients were enrolled. At level 1 (amrubicin 40 mg/m and carboplatin AUC 4.0), all three patients experienced DLTs (grade 4 neutropenia > or =4 days, thrombocytopenia <20,000/mm, or grade 3 diarrhea), and this dose level was determined to be the MTD. At the reduced dose of level 0 (amrubicin 35 mg/m and carboplatin AUC 4.0), although DLTs were observed in three of the nine patients, they were considered to be clinically not severe and could be managed. Non-hematological toxicities were mild or moderate and reversible. The objective response rate was 83%, and the median survival time was 12.7 months.

CONCLUSIONS: The MTD of this combination was amrubicin 40 mg/m and carboplatin AUC 4.0, and the recommended dose for a phase II trial is a combination of amrubicin 35 mg/m and carboplatin AUC 4.0. We are now conducting a multicenter phase II trial of this regimen to determine the activity of this combination for elderly patients with SCLC.