OBJECTIVES: The FDA-approved dosing schedule of docetaxel for NSCLC is 75 mg/m² every 21 days; however, prescribers often modify the dose and schedule to manage toxicity. This meta-analysis was designed to identify and compare survival and toxicity outcomes of randomized controlled trials (RCTs) evaluating dose and frequency variations of docetaxel.

METHODS: A systematic literature review was conducted to identify eligible RCTs written in English, that included patients with NSCLC, reported at least one survival or drug toxicity outcome, and varied docetaxel dose or duration between treatment groups. The search was conducted in 2016, with a subsequent evaluation to identify more recent articles from 2016-2018. Studies were excluded if other factors varied between treatment arms. Data were extracted by two independent reviewers and analyzed using CMA (Comprehensive Meta-Analysis V3, USA) by pooling reported statistics using the DerSimonian and Laird random effects model. Sensitivity analyses and assessments for heterogeneity and publication bias were conducted.

RESULTS: Fourteen publications met eligibility criteria, primarily evaluating weekly versus every 21-day schedules and 75 versus 100 mg/m². There were no statistically significant differences in 1-year survival or response rates for the weekly versus every 21-day schedule (odds ratio[OR]=0.93, 95% confidence interval [CI]: 0.55-1.55, p=0.77), or for the 75 versus 100 mg/m² dose (OR=0.77, 95% CI: 0.37-1.56, p=0.46). There were significantly lower odds of neutropenia (OR=0.12, 95% CI: 0.07-0.22, p<0.001), febrile neutropenia (OR=0.13, 95% CI: 0.05-0.40, p<0.001), and leukopenia (OR=0.19, 95% CI: 0.08-0.44, p<0.001) with the weekly schedule, and the 75 mg/m² dose was associated with lower neutropenia (OR=0.33, 95% CI: 0.22-0.49, p<0.001), fatigue/asthenia (OR=0.55, 95% CI: 0.31-0.95, p=0.03), and infection (OR=0.097, 95% CI: 0.012-0.77. p=0.03) versus 100 mg/m². Results remained consistent across sensitivity analyses.

CONCLUSIONS: This meta-analysis suggests that lower docetaxel dose with a more frequent schedule may reduce patient toxicity without a negative impact on efficacy.