Commentary: Chemotherapy Dosing in Obese Patients With Cancer—The Need for Evidence-Based Clinical Practice Guidelines

Chemotherapy dosing in adult cancer patients has been based, largely by convention, on a patient's estimated body-surface area, despite very few supporting data. At the same time, substantial preclinical and clinical evidence suggests that reductions in standard dose–intensity chemotherapy may compromise disease-free and overall survival in the curative setting.^1–4 In practice, however, the delivery of full standard dose–intensity chemotherapy is often not achieved for fear of excessive toxicity, particularly in overweight and obese patients.^5,6 Concerns about overdosing the obese cancer patient on the basis of actual body weight appear to be unfounded, with obese patients often experiencing less, rather than more, hematologic toxicity.^5,7–9 Pharmacokinetic studies have demonstrated that chemotherapy dose calculations should generally be based on actual rather than ideal body weight.¹⁰ It has been suggested, in fact, that chemotherapy-associated neutropenia may be considered a surrogate pharmacokinetic marker for drug exposure, as multiple studies have shown that neutropenic events during a course of chemotherapy may result in improved disease-free or overall survival years later.^11,12

The retrospective study reported by Lopes-Serrao et al¹³ in this issue of JOP highlights the common practice of chemotherapy dose capping in obese patients who receive cancer chemotherapy. Treatment duration and hematologic toxicity were compared between obese patients receiving cancer chemotherapy based on capping at a body-surface area of 2.2 m² and healthy weight patients. Despite receiving more cycles of treatment, there was a nonsignificant lower risk of hematologic toxicity in the obese patients, suggesting that there was room to increase the dose above the commonly used 2.0 m² cap. Because this was a relatively small, nonrandomized clinical trial and a number of factors may influence the decision to cap systemic chemotherapy, some differences in the two patient groups are apparent. The multivariate regression model is not especially helpful because of the small number of patients and relatively large number of covariates included. However, the results do illustrate the varying practice in oncology when it comes to dosing chemotherapy in obese patients.⁵ The results are also consistent with several previous studies demonstrating that the risk of hematologic toxicities in obese cancer patients receiving full- or near full-dose chemotherapy is no greater than that in healthy weight patients receiving full weight–based dosing.^9,11,14–16

Continuing confusion concerning optimal dosing in obese patients with cancer, along with increasing rates of obesity in the United States and the consistently poorer life expectancy in the severely obese patient with cancer has prompted ASCO to develop evidence-based clinical practice guidelines on appropriate chemotherapy dosing for obese adult patients with cancer. After a systematic review of the medical literature on this topic, a panel of experts from a broad range of related disciplines was assembled to address several common questions faced by oncologists in everyday practice when treating an obese patient with chemotherapy. These questions will include, among several others: Is there evidence that full weight–based dosing increases toxicity among obese patients with cancer? Is there evidence that less than full weight–based dosing compromises efficacy among obese cancer patients? Should chemotherapy dose modification for severe toxicity be any different in obese patients than in healthy weight patients? Are the answers to these questions dependent on the particular chemotherapeutic agent, age, major comorbidities, and treatment intent? While providing practical evidence-based recommendations related to these and other relevant questions, the panel is also likely to highlight the need for more research, both retrospective and prospective, to address a range of additional issues for which data are sparse or completely lacking.

Although excitement around emerging and expanding indications for novel targeted therapies continues to grow, it is apparent that the optimal use of many of these new agents is in combination with, rather than instead of, conventional myelosuppressive cytotoxic agents. Improving the delivery and dosing of conventional chemotherapeutic agents both alone or as adjuncts to novel biologic and molecular therapies in obese patients with cancer represents an extremely important strategy for the optimal care and treatment of patients with cancer. The forthcoming evidence-based clinical practice guidelines for chemotherapy dosing in the increasing population of obese patients with cancer should reduce persistent confusion and uncertainty around this topic, which have resulted in widespread practice and individual variation, and lead to more consistent dosing and improved clinical outcomes in this setting.

Author's Disclosures of Potential Conflicts of Interest

The author has indicated no potential conflicts of interest.