Model-based Meta-analysis for Quantifying Paclitaxel Dose Response in Cancer Patients

Model-based meta-analysis of dose response is a sophisticated method to guide dose and regimen selection. In this report, the effects of paclitaxel dose and regimen (weekly or every 3 weeks) on the efficacy and safety in cancer patients were quantified by model-based meta-analysis of 29 monotherapy trials. Logistic regression models were developed to assess the relationship between dose and objective response rate or neutropenia rate. Survival models were developed to assess the relationship between dose and overall survival or progression-free survival. Paclitaxel efficacy (e.g., objective response rate, median overall survival, and progression-free survival) is correlated with average dose per week (mg/m²/week), whereas safety (e.g., neutropenia rate) is correlated with dose per administration (mg/m²). Weekly paclitaxel regimen at 65-80 mg/m² is supported to have comparable to better efficacy and lower neutropenia incidence than an every-3-week regimen at 175 mg/m².