Department of Medical Oncology and Trials and Statistics, Erasmus University Medical Center, Rotterdam, the Netherlands.
Clin Cancer Res. 2012 Aug 15;18(16):4425-32. doi: 10.1158/1078-0432.CCR-12-0728. Epub 2012 May 29.
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.
众所周知，香烟烟雾会影响几种抗癌药物的代谢。它还可能影响不良事件的发生率和严重程度以及化疗的疗效。本研究的主要目的是研究吸烟对接受多西紫杉醇或紫杉醇治疗的患者的药代动力学和毒性的影响。
对 566 名接受多西紫杉醇或紫杉醇治疗的患者（429 名非吸烟者和 137 名吸烟者）的吸烟状况、毒性谱和药代动力学参数（通过非线性混合效应模型群体分析计算）进行了测定。
与非吸烟者相比，接受多西紫杉醇治疗的吸烟者发生 4 级中性粒细胞减少症的比例较低（35%比 52%；P = 0.01）。接受紫杉醇治疗的吸烟者白细胞减少症（3 级和 4 级）的发生率低于非吸烟者（12%比 25%；P = 0.03），非吸烟者的白细胞（WBC）最低点较低（中位数，2.7×10（9）/L；范围，0.05×10（9）至 11.6×10（9）/L）低于吸烟者（中位数，3.3×10（9）/L；范围 0.8×10（9）至 10.2×10（9）/L；P = 0.02）。有趣的是，与接受紫杉醇治疗的非吸烟者相比，基线时 WBC 计数和绝对中性粒细胞计数明显较低（P = 0.0001）。吸烟者和非吸烟者的两种紫杉烷的药代动力学参数相似。
吸烟不会改变多西紫杉醇和紫杉醇的药代动力学决定因素。接受多西紫杉醇和紫杉醇治疗的吸烟者中性粒细胞减少症和白细胞减少症较少，但需要进一步研究来阐明这种潜在的保护作用。
