Invloed van roken op farmacokinetiek en toxiciteit van taxanen

OBJECTIVE: To examine the effects of smoking on the pharmacokinetics and toxicities of patients treated with docetaxel or paclitaxel. Cigarette smoke is known to interact with the metabolism of several anticancer drugs. It may also affect the incidence and severity of adverse events and the efficacy of chemotherapy. METHODS: Smoking status, toxicity profiles, and pharmacokinetic parameters (calculated by nonlinear mixed-effect modelling population analysis) were determined in 566 patients (429 non-smokers and 137 smokers) treated with docetaxel or paclitaxel. RESULTS: Smokers treated with docetaxel showed less grade 4 neutropenia (35% vs. 52%; P = 0.01) than non-smokers. Smokers treated with paclitaxel had less grade 3/4 leukopenia than non-smokers (12% vs. 25%; P = 0.03), and the white blood cell (WBC) nadir was lower in non-smokers (median 2.7 × 10⁹/L, range 0.05 × 10⁹/L-11.6 × 10⁹/L) than in smokers (median 3.3 × 10⁹/L, range 0.8 × 10⁹/L-10.2 × 10⁹/L; P = 0.02). Of interest, significantly lower WBC counts and absolute neutrophil counts at baseline were seen in non-smoking patients treated with paclitaxel (P = 0.0001). Pharmacokinetic parameters were similar in smokers and non-smokers for both taxanes. CONCLUSION: Cigarette smoking does not alter the pharmacokinetic determinants of docetaxel and paclitaxel. Smokers treated with docetaxel and paclitaxel have less neutropenia and leukopenia, but further research is warranted to elucidate this potential protective effect.