Dosing Considerations for Obese Patients Receiving Cancer Chemotherapeutic Agents

OBJECTIVE: To examine the available trials evaluating the effect of obesity on the pharmacokinetic parameters of chemotherapy agents. DATA SOURCE: 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. DATA SELECTION AND DATA EXTRACTION: All articles were critically evaluated, and all pertinent information was included. Studies were included if they addressed obesity and pharmacokinetic parameters. DATA SYNTHESIS: 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. CONCLUSION: Some cytotoxic agents used in practice have altered pharmacokinetics in obese patients. Studies prospectively validating dose individualization for obese patients are needed.