Increasing dose intensity of cisplatin-etoposide in advanced nonsmall cell lung carcinoma -: A phase III randomized trial of the Spanish Lung Cancer Group

BACKGROUND. The authors designed this randomized, controlled trial to assess whether dose intensification of a cisplatin-etoposide combination (PE), achieved by shortening the interval between chemotherapy cycles, would improve response rate and survival. The maximum tolerated dose of PE was administered in either 3- or 4-week cycles to patients with advanced nonsmall cell lung carcinoma (NSCLC). METHODS, One hundred twenty-three patients were randomized into two groups. The dose-intense arm received cisplatin 35 mg/m(2) and etoposide 200 mg/m(2) on Days 1-3 every 4 weeks. The dose-dense arm received the same schedule every 3 weeks along with 5 mu g/kg of recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) administered subcutaneously on Days 4-13. RESULTS. Patient characteristics were well balanced in both treatment arms. Fifty-four percent of patients were classified as Stage IIIB. A 32% increase in relative dose intensity was achieved in the dose-dense arm compared with the dose-intense arm. The response rates were 32% in the dose-intense arm and 27% in the dose-dense arm (P = 0.9). The median overall survival was higher in the dose-dense arm, 9 Versus 7.2 months (P = 0.2). The main toxicity was myelosuppression, although the administration of GM-CSF significantly reduced the percentage of patients with Grade 4 granulocytopenia (53% vs. 78%). Fifty-four percent of the patients in the dose-intense arm and 35% of those in the dose-dense arm developed febrile neutropenia (P = 0.07). There were ten (8%) treatment-related deaths, three (4%) in the dose-intense arm and seven (12%) in the dose-dense arm (P = 0.3); three deaths in each arm were due to febrile neutropenia. CONCLUSIONS. The dose-intensification achieved in the dose-dense PE regimen did not correlate with significant improvements in response rate or survival and cannot be recommended in the light of the diversity of new drug combinations available today. However, the use of rhGM-CSF significantly reduced the incidence of severe granulocytopenia. (C) 1999 American Cancer Society.