Carboplatin in association with etoposide and either adriamycin or epirubicin for untreated small cell lung cancer: A dose escalation study of carboplatin

Abstract

A multi-center, open trial was conducted to determine the maximal tolerable dose of carboplatin in combination with conventional doses of both etoposide and an anthracycline for the treatment of previously untreated small cell lung cancer (SCLC) patients. Ninety-five patients [48 with limited disease (LD) and 47 with extensive disease (ED)¦ received a total of 376 courses of treatment. Carboplatin was given on day 1 at a dose of 250 mg m⁻² in 60 courses, 300 mg m⁻² in 69, 330 mg m⁻² in 236 and 350 mg m^-2 in 11, with 120 mg m⁻² etoposide on days 1, 3 and 5 and either 40 mg m^-2 adriamycin or 60 mg m⁻² epirubicin on day 1. Epirubicin was not administered before carboplatin reached the dose of 330 mg m⁻². Courses were repeated every 3 weeks. The main toxicity was hematological. The first course of therapy induced a dose-dependent decrease of leucocyte, neutrophil and platelet counts: all patients, except one, who received 350 mg m⁻² carboplatin had a neutropenia below 200 μ⁻¹ and a thrombopenia below 100,000 μl⁻¹. Three patients died of septicemia. Other toxicities were well tolerated. After three courses, patients were re-staged by performing a mandatory fiberoptic bronchoscopy and a thoracic computed axial tomography (CAT). The overall objective response rate for 86 evaluable patients was 91% (98% for LD) with 21% complete remissions (30% for LD). All 23 hepatic and six brain sites, evaluable after chemotherapy alone, responded. This new combination, in which the recommended dose of carboplatin is 330 mg m⁻², should be evaluated in a prospective study for SCLC.