Influence of smoking on the pharmacokinetics and toxicity profiles of taxane therapy.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Medical Oncology and Trials and Statistics, Erasmus University Medical Center, Rotterdam, the Netherlands. a.degraan@erasmusmc.nl
Anne-Joy M
AJ
de Graan
Walter J
WJ
Loos
Lena E
LE
Friberg
Sharyn D
SD
Baker
Jessica M
JM
van der Bol
Leni
L
van Doorn
Erik A C
EA
Wiemer
Bronno
B
van der Holt
Jaap
J
Verweij
Ron H J
RH
Mathijssen
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012189:Retrospective Studies; D012907:Smoking; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D055815:Young Adult
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel