Appropriate Chemotherapy Dosing for Obese Adult Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline.

Abstract

More than 60% of adults in the United States have a body mass index (BMI) over 25 and are considered overweight or obese. Clinicians traditionally order chemotherapy doses based on a patient's estimated body-surface area (BSA) using formulas that were developed decades ago. Despite studies confirming the safety and importance of full weight–based chemotherapy dosing, many overweight and obese patients receive limited chemotherapy doses that are not based on actual weight. When chemotherapy doses are calculated according to actual body weight, and delivered to obese patients, they are less likely to experience toxicity and/or bone marrow suppression. Although poorer outcomes among obese patients are most likely multifactorial, systemic chemotherapy at less than full weight–based dosing and unnecessary dose reductions may partially explain the significantly higher cancer mortality rates observed in overweight and obese individuals. Underdosing of chemotherapy is of particular concern in patients with chemotherapy-responsive and potentially curable malignancies; reductions in standard chemotherapy dose intensity may increase the risk of disease recurrence and mortality. With these issues in mind, ASCO recently published a new clinical practice guideline on appropriate chemotherapy dosing for obese adult patients with cancer, in Journal of Clinical Oncology.1 The guideline is based on a systematic search and review of the literature. An expert panel considered literature identified by the systematic review. Details are provided in the full guideline and its Data Supplements. The primary efficacy outcomes of interest included overall, disease-specific, disease-free, relapse-free, event-free, and progression-free survival. Treatment-related toxicities were also a primary outcome. In addition to abundant preclinical studies, clinical evidence in support of this guideline comes from several randomized controlled trials (RCTs) comparing delivered dose intensity, retrospective analyses of RCTs and cohort studies, as well as pharmacokinetic studies. THE BOTTOM LINE Appropriate Chemotherapy Dosing for Obese Adult Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Intervention Recommendations for appropriate chemotherapy dosing for obese adult patients with cancer Target Audience Medical oncologists, pharmacists, oncology nurses Key Recommendations Panel recommends that full weight–based chemotherapy doses be used in the treatment of the obese patient with cancer, particularly when the goal of treatment is cure. Clinicians should respond to all treatment-related toxicities in obese patients with cancer in the same ways they do for nonobese patients. If a dose reduction is used in response to toxicity, consideration should be given to the resumption of full weight–based doses for subsequent cycles, especially if a possible cause for the toxicity (eg, impaired renal, hepatic function) has been resolved. There is no evidence to support the need for greater dose reductions for obese patients compared with nonobese patients. The use of fixed-dose cytotoxic chemotherapy is rarely justified (except for a few select agents). Methods Systematic review of medical literature and analysis of the medical literature by the update committee of an expert panel Additional Information The recommendations, clinical questions, and a brief summary of the literature and discussion are in the JCO Guideline publication (http://jco.ascopubs.org/content/early/2012/03/27/JCO.2011.39.9436/suppl/DC1). The full guideline, with comprehensive discussions of the literature, methodology, full reference list, evidence tables, and clinical tools and resources, can be found at www.asco.org/guidelines/wbd. A commentary by Gary H. Lyman is available at http://jop.ascopubs.org/content/early/2012/04/03/JOP.2012.000606.full.pdf+html