Influence of Smoking on the Pharmacokinetics and Toxicity Profiles of Taxane Therapy

Purpose: Cigarette smoke is known to interact with the metabolism of several anti-cancer drugs. It may also affect the incidence and severity of adverse events and efficacy of chemotherapy. The main objective of this study was to examine the effects of smoking on the pharmacokinetics and toxicities of patients treated with docetaxel or paclitaxel. Experimental Design: Smoking status, toxicity profiles, and pharmacokinetic parameters (calculated by non-linear mixed effect modeling 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% versus 52%; P = 0.01) than non-smokers. Smokers treated with paclitaxel had less grade 3-4 leukopenia than non-smokers (12% versus 25%; P = 0.03) and the WBC nadir was lower in non-smokers (median 2.7 ×109/L; range 0.05 -11.6 x109/L) than in smokers (median 3.3 x109/L; range 0.8 -10.2 x109/L; P = 0.02). Of interest, significantly lower white blood cell 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. Conclusions: Cigarette smoking does not alter the pharmacokinetic determinants of docetaxel and paclitaxel. Smokers treated with docetaxel and paclitaxel have less neutropenia and leucopenia, but further research is warranted to elucidate this potential protective effect.