Hall Ronald G, Jean Gary W, Sigler Meredith, Shah Sachin
Texas Tech University Health Sciences Center, Dallas, TX, USA.
Ann Pharmacother. 2013 Dec;47(12):1666-74. doi: 10.1177/1060028013509789. Epub 2013 Nov 4.
To examine the available trials evaluating the effect of obesity on the pharmacokinetic parameters of chemotherapy agents.
A PubMed search (January 1977-June 2013) was conducted for English-language articles evaluating obesity and its relationship to pharmacokinetic parameters of chemotherapy agents. Search terms included: chemotherapy, obesity, excess weight, overweight, neoplasm, pharmacokinetics, dosing, cancer, body mass index, toxicity, efficacy, body surface area.
All articles were critically evaluated, and all pertinent information was included. Studies were included if they addressed obesity and pharmacokinetic parameters.
Obesity and cancer are preeminent health care challenges in the 21st century, with obese persons being at an increased risk of cancer. Given this background, it is troubling that limited information is available for dosing chemotherapy agents in obese patients. Pharmacokinetic parameters of other drug classes have been affected by increased weight. It is important to evaluate the effect on chemotherapy agents given their narrow therapeutic window. Dose capping has been used to limit excess toxicity in obese patients at the risk of providing a less-effective regimen. Data suggest an increased dose of carboplatin, cisplatin, ifosfamide, paclitaxel, and vincristine may be needed in obese patients. The literature also suggests that no dosing alteration may be necessary for obese patients receiving topoisomerase I and II inhibitors, 5-fluorouracil, methotrexate, and docetaxel. A dose decrease might be suitable for cyclophosphamide.
Some cytotoxic agents used in practice have altered pharmacokinetics in obese patients. Studies prospectively validating dose individualization for obese patients are needed.
考察评估肥胖对化疗药物药代动力学参数影响的现有试验。
对PubMed（1977年1月至2013年6月）进行检索，以查找评估肥胖及其与化疗药物药代动力学参数关系的英文文章。检索词包括：化疗、肥胖、超重、体重过重、肿瘤、药代动力学、给药剂量、癌症、体重指数、毒性、疗效、体表面积。
对所有文章进行严格评估，并纳入所有相关信息。纳入涉及肥胖和药代动力学参数的研究。
肥胖和癌症是21世纪突出的医疗保健挑战，肥胖者患癌症的风险增加。鉴于此背景，令人担忧的是，关于肥胖患者化疗药物给药剂量的信息有限。其他药物类别的药代动力学参数已受体重增加影响。鉴于化疗药物治疗窗狭窄，评估其影响很重要。剂量限制已被用于限制肥胖患者的过度毒性，但存在提供疗效较差方案的风险。数据表明，肥胖患者可能需要增加卡铂、顺铂、异环磷酰胺、紫杉醇和长春新碱的剂量。文献还表明，接受拓扑异构酶I和II抑制剂、5-氟尿嘧啶、甲氨蝶呤和多西他赛的肥胖患者可能无需调整给药剂量。环磷酰胺可能适合减少剂量。
实践中使用的一些细胞毒性药物在肥胖患者中的药代动力学发生了改变。需要进行前瞻性研究以验证肥胖患者的剂量个体化。
