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

• Published in: Clinical cancer research Vol. 18; no. 16; pp. 4425 - 4432
• Main Authors: DE GRAAN, Anne-Joy M, LOOS, Walter J, FRIBERG, Lena E, BAKER, Sharyn D, VAN DER BOL, Jessica M, DOORN, Leni Van, WIEMER, Erik A. C, DER HOLT, Bronno Van, VERWEIJ, Jaap, MATHIJSSEN, Ron H. J
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.08.2012
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Biological and medical sciences; Female; Humans; Leukopenia - chemically induced; Male; Medical sciences; Middle Aged; Neoplasms - complications; Neoplasms - drug therapy; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Paclitaxel - pharmacokinetics; Pharmacology. Drug treatments; Retrospective Studies; Smoking; Taxoids - administration & dosage; Taxoids - adverse effects; Taxoids - pharmacokinetics; Tobacco, tobacco smoking; Toxicology; Young Adult; Treatment; Pharmacokinetics; Toxicity; Taxane derivatives; Profile; Tobacco smoking
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.ccr-12-0728

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 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. Smoking status, toxicity profiles, and pharmacokinetic parameters (calculated by nonlinear mixed-effect modeling population analysis) were determined in 566 patients (429 nonsmokers and 137 smokers) treated with docetaxel or paclitaxel. Smokers treated with docetaxel showed less grade IV neutropenia (35% vs. 52%; P = 0.01) than nonsmokers. Smokers treated with paclitaxel had less grade III-IV leukopenia than nonsmokers (12% vs. 25%; P = 0.03), and the white blood cell (WBC) nadir was lower in nonsmokers (median, 2.7 × 10(9)/L; range, 0.05 × 10(9) to 11.6 × 10(9)/L) than in smokers (median, 3.3 × 10(9)/L; range 0.8 × 10(9) to 10.2 × 10(9)/L; P = 0.02). Of interest, significantly lower WBC counts and absolute neutrophil counts at baseline were seen in nonsmoking patients treated with paclitaxel (P = 0.0001). Pharmacokinetic parameters were similar in smokers and nonsmokers for both taxanes. 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.