Hunter Rodney J, Navo Marisa A, Thaker Premal H, Bodurka Diane C, Wolf Judith K, Smith Judith A
Division of Pharmacy, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77230, USA.
Cancer Treat Rev. 2009 Feb;35(1):69-78. doi: 10.1016/j.ctrv.2008.07.005. Epub 2008 Oct 14.
Obesity is a chronic disease that has increased dramatically in the past few decades worldwide. More concerning, obesity is linked to many other disease states including cancer and has been shown to increase mortality. Unfortunately, oncology drug development and most clinical trials fail to address the problem of appropriate chemotherapy dosing in obese patients. This can potentially lead to either increased toxicity or decreased efficacy. Although dosing schemas may vary among practices and institutions, many oncologists tend to remain conservative and empirically dose-reduce obese patients despite data suggesting otherwise. The goals of this review were to consider the various aspects of pharmacokinetics in obese patients, to examine the existing literature regarding chemotherapy dosing in obese patients, and to determine the most appropriate weight estimation for body surface area (BSA) dose calculations. Based upon the current clinical data of obesity and chemotherapy dosing it can be concluded there is very limited if any data to support the perception that capping the doses of obese patients is beneficial and more likely this practice may have negative implications on survival outcomes. Under dosing patients with treatable or even curable disease to prevent toxicities could be costing the obese oncology patient population months to years of overall survival.
肥胖是一种慢性疾病,在过去几十年里在全球范围内急剧增加。更令人担忧的是,肥胖与包括癌症在内的许多其他疾病状态相关联,并且已被证明会增加死亡率。不幸的是,肿瘤药物研发以及大多数临床试验都未能解决肥胖患者化疗剂量的合适问题。这可能会导致毒性增加或疗效降低。尽管不同的医疗机构和临床实践中的给药方案可能有所不同,但许多肿瘤学家倾向于保持保守态度,根据经验减少肥胖患者的剂量,尽管有数据表明并非如此。本综述的目的是考虑肥胖患者药代动力学的各个方面,研究关于肥胖患者化疗给药的现有文献,并确定用于计算体表面积(BSA)剂量的最合适体重估计方法。根据目前关于肥胖和化疗给药的临床数据可以得出结论,几乎没有数据支持限制肥胖患者剂量有益的观点,而且这种做法更有可能对生存结果产生负面影响。为预防毒性而对患有可治疗甚至可治愈疾病的患者进行低剂量给药,可能会使肥胖肿瘤患者群体损失数月至数年的总生存期。