Chemotherapy for Elderly Patients With Advanced Non-Small-Cell Lung Cancer: The Multicenter Italian Lung Cancer in the Elderly Study (MILES) Phase III Randomized Trial

TLDR

Vinorelbine and gemcitabine are known to prolong survival and improve quality of life in elderly patients with advanced non‑small‑cell lung cancer. The study aimed to compare the effectiveness and toxicity of vinorelbine plus gemcitabine versus each drug alone in a randomized phase III trial of patients aged 70 and older with advanced NSCLC. Patients were randomized to receive intravenous vinorelbine (30 mg/m²), gemcitabine (1200 mg/m²), or the combination (vinorelbine 25 mg/m² plus gemcitabine 1000 mg/m²) on days 1 and 8 every 3 weeks for up to six cycles, with survival as the primary endpoint and quality of life and toxicity as secondary endpoints. The combination therapy did not improve survival (HR 1.17 vs vinorelbine, HR 1.06 vs gemcitabine), produced similar quality of life, but was more toxic than either single agent.

Abstract

Vinorelbine prolongs survival and improves quality of life in elderly patients with advanced non-small-cell lung cancer (NSCLC). Some studies have also suggested that gemcitabine is well tolerated and effective in such patients. We compared the effectiveness and toxicity of the combination of vinorelbine plus gemcitabine with those of each drug given alone in an open-label, randomized phase III trial in elderly patients with advanced NSCLC.Patients aged 70 years and older, enrolled between December 1997 and November 2000, were randomly assigned to receive intravenous vinorelbine (30 mg/m(2) of body surface area), gemcitabine (1200 mg/m(2)), or vinorelbine (25 mg/m(2)) plus gemcitabine (1000 mg/m(2)). All treatments were delivered on days 1 and 8 every 3 weeks for a maximum of six cycles. The primary endpoint was survival. Survival curves were drawn using the Kaplan-Meier method and analyzed by the Mantel-Haenszel test. Secondary endpoints were quality of life and toxicity.Of 698 patients available for intention-to-treat analysis, 233 were assigned to receive vinorelbine, 233 to gemcitabine, and 232 to vinorelbine plus gemcitabine. Compared with each single drug, the combination treatment did not improve survival. The hazard ratio of death for patients receiving the combination treatment was 1.17 (95% confidence interval [CI] = 0.95 to 1.44) that of patients receiving vinorelbine and 1.06 (95% CI = 0.86 to 1.29) that of patients receiving gemcitabine. Although quality of life was similar across the three treatment arms, the combination treatment was more toxic than the two drugs given singly.The combination of vinorelbine plus gemcitabine is not more effective than single-agent vinorelbine or gemcitabine in the treatment of elderly patients with advanced NSCLC.