Improving survival without reducing quality of life in small-cell lung cancer patients by increasing the dose-intensity of chemotherapy with granulocyte colony-stimulating factor support: Results of a British medical research council multicenter randomized trial

Purpose: The treatment of small-cell lung cancer patients with good perform ance status aims to improve survival. Dose-intensification could be a way t o achieve improved survival but can be limited by neutropenia and thrombocy topenia. Preliminary, nonrandomized feasibility studies showed that doxorub icin, cyclophosphamide, and etoposide (ACE) could be given every 2 (instead of the usual 3) weeks with granulocyte colony-stimulating factor (G-CSF) ( lenograstim; Chugai-Rhone-Poulenc. Tokyo, Japan) support. The present multi center randomized trial was designed to examine whether such dose-intensifi cation improves survival while maintaining acceptable toxicity levels. Patients and Methods: All patients were randomized to receive six cycles of ACE either every 3 weeks (control [C] group) or every 2 weeks with G-CSF ( G group). The standard dose-intensity of ACE was increased by 50% in group G. Results: Four hundred and three patients (G group: group: n = 202) were ran domized. The received dose-intensity was 34% higher in the G group than in the C group, Complete response rates were 40% for the G group and 28% for t he C group (P = .02), and overall rates were 78% for the G group and 79% fo r the C group. Survival was longer in the G group (hazard ratio = 0.80; 95% confidence interval, 0.65 to 0.99; P =.04), survival rates for the G and C groups being 47% and 39% at 12 months and 13% and 8% at 24 months, respect ively. Metastasis-free survival, nonhematologic toxicity, and quality of li fe were similar in the two groups. In the G group, there was less neutropen ia but more thrombocytopenia and more frequent blood and platelet transfusi ons. Conclusion: Increasing the dose-intensity of ACE with G-CSF support improve d survival while maintaining acceptable toxicity. (C) 2000 by American Soci ety of Clinical Oncology.