MULTIPLE-DRUG WEEKLY CHEMOTHERAPY VERSUS STANDARD COMBINATION REGIMEN IN SMALL-CELL LUNG-CANCER - A PHASE-III RANDOMIZED STUDY CONDUCTED BY THE EUROPEAN LUNG-CANCER WORKING PARTY

Purpose: A randomized trial was conducted in patients with small-cell lung cancer (SCLC) to determine if survival can be improved by a weekly chemotherapy regimen combining various drugs. Patients and Methods: Two hundred twenty-three patients were randomized to receive either six courses of a multiple-drug combination (MDC) regimen (Adriamycin [ADR; doxorubicin; Farmitalia Carlo Erba, Milan, Italy] 25 mg/m2 intravenously [IV] on day 1; etoposide [VP16] 120 mg/m2 IV on day 1; cyclophosphamide [CPA] 500 mg/m2 IV on day 1; cisplatin 60 mg/m2 IV on day 8; vindesine [VDS] 3 mg/m2 IV on day 8; vincristine [VCR] 2 mg IV on day 15; methotrexate [MTX] 100 mg/m2 IV on day 15), or a standard chemotherapy (SC) regimen (ADR 50 mg/m2 IV on day 1; CPA 1 g/m2 IV on day 1; VP16 80 mg/m2 IV on days 1 to 3). Results: In 98 MDC-treated and 101 SC-treated assessable patients, we observed 69% and 62% objective responses rates, respectively. There was no significant difference in survival, with median durations and 2-year overall survival rates of 49 and 43 weeks and 8.5% and 7.9%, respectively. There was a significant increase in response rate in favor of MDC patients with limited disease (84% v 62%). Toxicity was tolerable, although SC was more hematotoxic, with 76% (v 59%) experiencing leukopenia and 17% (v 7%) experiencing thrombocytopenia (grades III and IV). If the cumulative doses received were nearly equal to the scheduled cumulative doses in both arms, the total relative dose-intensity (RDI) was significantly higher in the SC arm. The difference was due to increased treatment delays in the MDC arm. Conclusion: Weekly MDC failed to improve survival rates in patients with SCLC.