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

J Thorac Oncol. 2011 Dec;6(12):2090-6. doi: 10.1097/JTO.0b013e3182307e3c.

Abstract

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) 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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Infective Agents / therapeutic use*
  • Antibiotic Prophylaxis*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bacterial Infections / complications
  • Bacterial Infections / prevention & control*
  • Carboplatin / administration & dosage
  • Carboplatin / adverse effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Disease-Free Survival
  • Docetaxel
  • Double-Blind Method
  • Dyspnea / chemically induced
  • Female
  • Humans
  • Intention to Treat Analysis
  • Kaplan-Meier Estimate
  • Leukopenia / chemically induced
  • Levofloxacin*
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Neutropenia / complications
  • Ofloxacin / therapeutic use*
  • Pain / chemically induced
  • Taxoids / administration & dosage
  • Taxoids / adverse effects

Substances

  • Anti-Infective Agents
  • Taxoids
  • Docetaxel
  • Levofloxacin
  • Ofloxacin
  • Carboplatin