Comparative Effectiveness and Outcomes Research, Duke University and the Duke Cancer Institute, 2424 Erwin Road, Suite 205, Durham, NC 27705, USA.
Nat Rev Clin Oncol. 2013 Aug;10(8):451-9. doi: 10.1038/nrclinonc.2013.108. Epub 2013 Jul 16.
Retrospective and prospective preclinical and clinical data have demonstrated an association between chemotherapy dose intensity and both clinical efficacy and toxicity. The optimum tolerable and effective dose and schedule of chemotherapeutic agents is based on data from dose-finding studies and early clinical trials. There is considerable evidence that reductions in the recommended dose intensity often occurs in actual clinical practice, particularly among overweight and obese patients with cancer. With increasing rates of obesity, and variation and uncertainty about appropriate dosing of chemotherapy in obese patients, ASCO has generated clinical practice guidelines for appropriate chemotherapy dosing for obese adult patients with cancer. Without evidence of any increase in treatment-related toxicity among obese patients receiving chemotherapy, the guidelines recommend that, after considering any accompanying comorbidities, chemotherapy dosing should be calculated based on body surface area using actual weight, rather than an estimate or idealization of weight. While further research is needed, pharmacokinetic studies support the use of actual body weight to calculate chemotherapy doses for most chemotherapy drugs in obese patients. We highlight the issue of chemotherapy dosing in this population, how a more personalized approach can be achieved, as well as discussing areas for further research.
回顾性和前瞻性临床前和临床数据表明，化疗剂量强度与临床疗效和毒性之间存在关联。化疗药物的最佳耐受和有效剂量和方案是基于剂量发现研究和早期临床试验的数据。有大量证据表明，在实际临床实践中，推荐的剂量强度经常降低，尤其是在超重和肥胖的癌症患者中。随着肥胖率的增加，以及肥胖患者化疗剂量的变化和不确定性，美国临床肿瘤学会（ASCO）为肥胖成年癌症患者制定了适当化疗剂量的临床实践指南。肥胖患者接受化疗时，没有证据表明治疗相关毒性增加，因此指南建议，在考虑任何伴随的合并症后，应根据实际体重使用体表面积计算化疗剂量，而不是估计或理想化体重。虽然还需要进一步的研究，但药代动力学研究支持在肥胖患者中使用实际体重来计算大多数化疗药物的化疗剂量。我们强调了这一人群中的化疗剂量问题，如何实现更个性化的方法，并讨论了进一步研究的领域。
