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Chemotherapy dosing in overweight and obese patients with cancer

Abstract

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.

Key Points

  • Increasing obesity rates represent a global public health problem that increases the risk of many diseases and conditions, including cancer

  • Chemotherapy dosing in adult cancer patients is generally based on body surface area; data suggest that obese patients receiving full chemotherapy doses do not experience greater toxicity than healthy weight individuals

  • Overweight and obese patients with cancer are often undertreated because arbitrary limits are used to calculate the dose of systemic chemotherapeutic agents

  • Retrospective and prospective clinical trial data suggest that reductions in delivered chemotherapy dose intensity is associated with increased rates of disease recurrence and cancer-associated mortality

  • Clinical practice guidelines have been developed for appropriate dosing of chemotherapy in adult patients that should enhance the quality of patient care and improve clinical outcomes

  • Further research on the application of pharmacokinetic and pharmacogenetic principles to chemotherapy dosing may enable more personalized treatment of obese patients with cancer

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Figure 1: Past and projected prevalence of overweight (BMI >25 kg/m2) individuals in the population.60
Figure 2: Mean relative dose intensity (RDI) of chemotherapy in women receiving chemotherapy for early stage breast cancer stratified by WHO BMI categories.73
Figure 3: Chemotherapy dosing in obese and non-obese patients with cancer.

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Both authors researched data for the article, made a substantial contribution to the discussion of the content and contributed equally to writing the article, including review and editing of the manuscript before submission.

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Correspondence to Gary H. Lyman.

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G. H. Lyman is co-chair and A. Sparreboom is a member of the ASCO Expert Panel involved in formulating the guidelines on appropriate chemotherapy dosing for obese adult patients with cancer.

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Lyman, G., Sparreboom, A. Chemotherapy dosing in overweight and obese patients with cancer. Nat Rev Clin Oncol 10, 451–459 (2013). https://doi.org/10.1038/nrclinonc.2013.108

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