Impact of obesity on chemotherapy management and outcomes in women with gynecologic malignancies

Objective. 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. Methods. 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. Results. 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. Conclusions. 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. (C) 2015 Elsevier Inc. All rights reserved.