Horowitz Neil S, Wright Alexi A
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, USA; Division of Medical Oncology, Dana Farber Cancer Institute, USA.
Division of Medical Oncology, Dana Farber Cancer Institute, USA.
Gynecol Oncol. 2015 Jul;138(1):201-6. doi: 10.1016/j.ygyno.2015.04.002. Epub 2015 Apr 12.
To describe the effects of obesity on the pharmacokinetics and dosing of chemotherapies and provide recommendations for chemotherapy management in obese women with gynecologic malignancies.
PubMEd and MEDLINE databases were searched for articles published before June 2014. Only English-language articles were considered. 84 manuscripts were reviewed and 66 were included. Search terms included: obesity, overweight, body mass index, body surface area, glomerular filtration rate, chemotherapy, ovarian cancer, endometrial cancer, inflammation, and pharmacokinetics,
Obese cancer patients have worse clinical outcomes, compared with non-obese patients. This may be because of differences in pharmacokinetics, metabolic dysregulation, or physicians' decisions to reduce chemotherapy dose-intensity during treatment to minimize toxicities. A 2012 American Society of Clinical Oncology Clinical Practice Guideline recommends using actual body weight for chemotherapy dosing in all patients treated with curative intent, irrespective of obesity, to avoid compromising clinical outcomes, including progression free survival (PFS) and overall survival (OS). In women with gynecologic cancers most studies demonstrate no difference in PFS or OS when obese patients receive the same chemotherapy dose intensity as non-obese patients, except perhaps with bevacizumab.
Chemotherapy dose-intensity is a critical determinant of cancer outcomes and should be maintained in all patients, irrespective of obesity. Future studies should prospectively examine the impact of obesity on clinical outcomes (adverse events, survival) to improve the care of this growing population of patients who are at risk for inferior clinical outcomes.
描述肥胖对化疗药物药代动力学及剂量的影响,并为肥胖的妇科恶性肿瘤患者的化疗管理提供建议。
检索PubMEd和MEDLINE数据库中2014年6月之前发表的文章。仅纳入英文文章。共检索84篇手稿,纳入66篇。检索词包括:肥胖、超重、体重指数、体表面积、肾小球滤过率、化疗、卵巢癌、子宫内膜癌、炎症和药代动力学。
与非肥胖癌症患者相比,肥胖癌症患者的临床结局更差。这可能是由于药代动力学差异、代谢失调,或医生在治疗期间为尽量减少毒性而决定降低化疗剂量强度。2012年美国临床肿瘤学会临床实践指南建议,对于所有接受根治性治疗的患者,无论是否肥胖,化疗给药均采用实际体重,以避免影响包括无进展生存期(PFS)和总生存期(OS)在内的临床结局。在妇科癌症女性患者中,大多数研究表明,肥胖患者与非肥胖患者接受相同化疗剂量强度时,PFS或OS无差异,但贝伐单抗可能除外。
化疗剂量强度是癌症结局的关键决定因素,所有患者均应维持该剂量强度,无论其是否肥胖。未来研究应前瞻性地研究肥胖对临床结局(不良事件、生存期)的影响,以改善对这一数量不断增加且临床结局可能较差的患者群体的治疗。