Division of Hematology-Oncology, Department of Medicine, University of Michigan, Ann Arbor, Mich., USA.
Oncology. 2013;85(4):216-22. doi: 10.1159/000355107. Epub 2013 Sep 24.
Chemotherapy-associated neutropenia has been reported to be a pharmacodynamic marker of response in some advanced solid tumors. Factors that accelerate drug clearance lead to lower plasma concentrations and toxicity, including neutropenia. Smoking accelerates the metabolism of several drugs, including chemotherapy. We sought to study the effects of smoking on gemcitabine-induced neutropenia in this retrospective study.
Smoking status and neutropenia along with other clinical parameters were recorded in 151 patients receiving first-line gemcitabine-based chemotherapy for advanced solid tumors.
Tumor types included breast (9.3%), lung (4.6%), pancreatobiliary (70.9%), or other/unknown primary cancer (15.2%). Logistic regression showed that never smokers had increased neutropenia versus current smokers (odds ratio: 3.5; 95% confidence interval, CI: 1.1-11.4). A 5-unit increase in pack-years reduced the odds of having higher neutropenia toxicity by 6.3% (95% CI 12 to 1%; p = 0.036).
Smokers had less neutropenia than nonsmokers, a finding that was more pronounced with increasing pack-years. This pharmacodynamic marker of gemcitabine-induced neutropenia may result in less efficacy of gemcitabine. Future prospective trials should correlate smoking, metabolizing phenotype, neutropenia, and response to gemcitabine therapy.
化疗相关性中性粒细胞减少症已被报道为某些晚期实体瘤反应的药效学标志物。加速药物清除的因素会导致较低的血浆浓度和毒性，包括中性粒细胞减少症。吸烟会加速包括化疗药物在内的几种药物的代谢。我们试图在这项回顾性研究中研究吸烟对吉西他滨引起的中性粒细胞减少症的影响。
在 151 名接受一线吉西他滨为基础的化疗治疗晚期实体瘤的患者中记录了吸烟状况和中性粒细胞减少症以及其他临床参数。
肿瘤类型包括乳腺癌（9.3%）、肺癌（4.6%）、胰胆（70.9%）或其他/未知原发性癌症（15.2%）。逻辑回归显示，从不吸烟者比现吸烟者更容易发生中性粒细胞减少症（优势比：3.5；95%置信区间，CI：1.1-11.4）。每增加 5 个吸烟包年，发生更高水平中性粒细胞减少症毒性的几率就会降低 6.3%（95%CI 12 到 1%；p=0.036）。
吸烟者的中性粒细胞减少症比不吸烟者少，而且随着吸烟包年数的增加，这种现象更为明显。这种吉西他滨引起的中性粒细胞减少症的药效学标志物可能会导致吉西他滨疗效降低。未来的前瞻性试验应将吸烟、代谢表型、中性粒细胞减少症和对吉西他滨治疗的反应相关联。
