Department of Medicine, Division of Hematology-Oncology, Ann Arbor, MI.
Taubman Health Sciences Library, Ann Arbor, MI.
J Thorac Oncol. 2014 Jul;9(7):917-926. doi: 10.1097/JTO.0000000000000191.
Cigarette smoke associated polycyclic aromatic hydrocarbons can induce key drug-metabolizing enzymes of cytochrome P450 and isoforms of the glucuronyl transferases families. These enzymes metabolize several systemic therapies for lung cancer. Induction of these enzymes may lead to accelerated clearance with resultant impact on systemic therapy efficacy and toxicity in smokers compared with nonsmokers. This article reviews published literature regarding the influence of smoking as it relates to alteration of metabolism of systemic therapy in lung cancer.
A structured search of the National Library of Medicine's PubMed/MEDLINE identified relevant articles. Data were abstracted and analyzed to summarize the findings.
Studies that analyzed pharmacokinetic data were prospective. Smokers receiving erlotinib exhibited rapid clearance, requiring a higher dose to reach equivalent systemic exposure compared with nonsmokers. Smokers receiving irinotecan also demonstrated increased clearance and lower systemic exposure. There was no difference in clearance of paclitaxel or docetaxel in smokers. Chemotherapy-associated neutropenia was worse in nonsmokers compared with smokers in patients treated with paclitaxel, docetaxel, irinotecan, and gemcitabine.
Systemic therapy for lung cancer has a narrow therapeutic index such that small changes in plasma concentrations or exposure in smokers may result in suboptimal therapy and poor outcomes. Smoking cessation must be emphasized at each clinical visit. However, prospective trials should take into consideration the effects of smoking history on drug pharmacokinetics and efficacy. The metabolizing enzyme phenotype in smokers may require individualized dose algorithms for specific agents.
香烟烟雾中含有的多环芳烃可诱导细胞色素 P450 家族的关键药物代谢酶和葡萄糖醛酸转移酶家族的同工酶。这些酶可代谢多种肺癌的全身治疗药物。这些酶的诱导可能导致清除加速，从而影响吸烟者与不吸烟者相比的全身治疗效果和毒性。本文综述了已发表的文献，探讨了吸烟对肺癌全身治疗药物代谢改变的影响。
通过美国国立医学图书馆的 PubMed/MEDLINE 进行结构化检索，以确定相关文章。提取和分析数据以总结发现。
分析药代动力学数据的研究是前瞻性的。接受厄洛替尼治疗的吸烟者表现出快速清除，需要更高的剂量才能达到与不吸烟者相当的全身暴露。接受伊立替康治疗的吸烟者也表现出清除率增加和全身暴露降低。在吸烟者中，紫杉醇或多西他赛的清除率没有差异。与吸烟者相比，接受紫杉醇、多西他赛、伊立替康和吉西他滨治疗的非吸烟者发生化疗相关中性粒细胞减少的情况更糟。
肺癌的全身治疗药物的治疗指数较窄，因此吸烟者血浆浓度或暴露量的微小变化可能导致治疗效果不佳和预后不良。必须在每次临床就诊时强调戒烟。然而，前瞻性试验应考虑吸烟史对药物药代动力学和疗效的影响。吸烟者的代谢酶表型可能需要针对特定药物制定个体化剂量算法。
