Randomized Phase III Trial of Docetaxel Plus Carboplatin with or without Levofloxacin Prophylaxis in Elderly Patients with Advanced Non-small Cell Lung Cancer The APRONTA Trial

Purpose: To examine the effect of levofloxacin prophylaxis on infection rates during chemotherapy with docetaxel plus carboplatin in elderly patients with advanced non-small cell lung cancer. Methods: In a randomized, double-blind, phase III study, patients (>= 65 years) with untreated, histologically/cytologically proven stage IIIB/IV non-small cell lung cancer received docetaxel (75 mg/m(2)) plus carboplatin (area under the curve 6) on day 1 every 3 weeks, plus once-daily levofloxacin (500 mg orally) or placebo on days 5 to 11. The primary end point was the rate of grade 3/4 infections or grade 1/2 infections treated with additional antibiotics. Secondary end points included overall infection rate, toxicity, overall survival, and progression-free survival. Results: In total, 187 patients were randomized to levofloxacin (n = 95) or placebo (n = 92). The rate of grade 3/4 infections or grade 1/2 infections treated with additional antibiotics (intent-to-treat population) was 27.5% (95% confidence interval, 19.3-39.0%) for levofloxacin versus 36.7% (95% confidence interval, 27.1-48.0%) for placebo. Median time to first infection was 67 days for levofloxacin versus 46 days for placebo. Grade 3/4 infections occurred in 8.8% of patients in the levofloxacin group versus 26.7% for placebo. There was one grade 5 infection in each group. Grade >= 3 toxicities (levofloxacin versus placebo) included leukopenia (63.2 versus 52.2%), neutropenia (62.1 versus 51.1%), dyspnea (12.6 versus 8.7%), and pain (10.5 versus 9.8%). There was no significant difference in overall survival or progression-free survival between groups. Conclusions: Levofloxacin prophylaxis reduces the rate of infection compared with placebo and is well tolerated in elderly patients receiving docetaxel plus carboplatin.