Andrew G. Renehan, Sacha Howell, and Anthony Howell, University of Manchester; Michelle Harvie and Anthony Howell, University Hospital of South Manchester NHS Foundation Trust, Manchester; Ramsey I. Cutress, University Hospitals Southampton; Ramsey I. Cutress, University of Southampton, Southampton, United Kingdom; Michael Leitzmann, University of Regensburg, Regensburg; and Tobias Pischon, Max Delbrück Center for Molecular Medicine (MDC), Berlin-Buch, Germany.
J Clin Oncol. 2016 Dec 10;34(35):4284-4294. doi: 10.1200/JCO.2016.69.1899. Epub 2016 Nov 7.
Purpose Obesity (body mass index [BMI] ≥ 30 kg/m) is common among patients with cancer. We reviewed management issues in the obese patient with cancer, focusing on how obesity influences treatment selection (including chemotherapy dosing), affects chemotherapy toxicity and surgical complications, and might be a treatment effect modifier. Methods The majority of evidence is drawn from observational studies and secondary analyses of trial data, typically analyzed in N × 3 BMI categories (normal weight, overweight, and obese) matrix structures. We propose a methodological framework for interpretation focusing on sample size and composition, nonlinearity, and unmeasured confounding. Results There is a common perception that obesity is associated with increased treatment-related toxicity. Accordingly, cytotoxic chemotherapy dose reduction is common in patients with elevated BMI. Contrary to this, there is some evidence that full dosing in obese patients does not result in increased toxicity. However, these data are from a limited number of regimens, and fail to fully capture cytotoxic drug pharmacodynamics and pharmacokinetic variability in obese patients. Among patients undergoing surgery, there is evidence that elevated BMI is associated with increased perioperative mortality and increased rates of infectious complications. A novel finding is that these relationships hold after surgery for malignancy, but not for benign indications. There are biologic plausibilities that obesity might be an effect modifier of treatment, but supporting evidence from clinical studies is inconsistent. Conclusion In line with the ASCO 2012 guidelines, chemotherapy dosing is probably best performed using actual body weight in obese patients. However, specific regimens known to be associated with increased toxicity in this group should be used with caution. There is no guidance on dose for obese patients treated with biologic agents. Currently, there are no specific recommendations for the surgical management of the obese patient with cancer.
目的 肥胖症（体重指数 [BMI]≥30kg/m）在癌症患者中较为常见。我们回顾了肥胖癌症患者的管理问题，重点关注肥胖如何影响治疗选择（包括化疗剂量）、影响化疗毒性和手术并发症，以及是否可能成为治疗效果的调节剂。
方法 大部分证据来自观察性研究和临床试验数据的二次分析，通常按 BMI 分为 N×3 个类别（正常体重、超重和肥胖）矩阵结构进行分析。我们提出了一种解释方法的框架，重点关注样本量和组成、非线性和未测量的混杂因素。
结果 人们普遍认为肥胖与治疗相关毒性增加有关。因此，超重患者的细胞毒性化疗剂量常被减少。然而，与这一观点相反，有一些证据表明肥胖患者给予全剂量不会导致毒性增加。但是，这些数据来自少数几种方案，并且不能完全捕捉肥胖患者细胞毒性药物的药效学和药代动力学的变异性。对于接受手术的患者，有证据表明，BMI 升高与围手术期死亡率增加和感染并发症发生率增加有关。一个新的发现是，这些关系在癌症手术后仍然存在，但在良性指征手术后则不存在。有生物学上的可能性表明肥胖可能是治疗的效应调节剂，但来自临床研究的支持证据并不一致。
结论 根据 ASCO 2012 指南，在肥胖患者中，化疗剂量最好使用实际体重进行。但是，对于与该组毒性增加相关的特定方案，应谨慎使用。对于接受生物制剂治疗的肥胖患者，目前没有关于剂量的指导。目前，对于肥胖癌症患者的手术管理尚无具体建议。
