A study published in the Journal of Clinical Oncologyin 2008 found that obesity is an important contributing factor to chemotherapy resistance and rising relapse rates in children with leukemia.1 According to the study, obese children diagnosed with leukemia have a 50% higher chance of relapsing compared to lean children with the cancer.
Investigating the mechanisms underlying this relationship between obesity and leukemia relapse, subsequent authors from the University of Southern California developed a mouse model, culturing fat and leukemia cells together, and then treating the leukemia cells with standard chemotherapy agents used in treating children, including vincristine, nilotinib (Tasigna), daunorubicin, and dexamethasone.2 The obese mice had higher relapse rates than the lean mice, and the researchers suggested that the leukemia cells in the relapsed mice were "hiding out" in the fat tissue during chemotherapy, effectively blocking the drugs from reaching the malignant cells.
Obesity is also generally linked with higher cancer incidences in both adults and children. "Obesity puts people in a chronic inflammatory state, and inflammation appears to promote cancer development," saidJennifer J. Griggs, MD, MPH, Associate Professor in the Departments of Internal Medicine and Health Management and Policy at the University of Michigan in Ann Arbor, and Co-Chair of ASCO's Guideline Expert Panel on Appropriate Chemotherapy Dosing for Obese Adult Patients with Cancer (see article).
Need for Additional Research
Because pediatric oncologists calculate chemotherapy doses in children based on their weight rather than on body surface area, as is used to measure dosing in adults with cancer, limited dosing does not appear to be as much of a concern in children. However, more research is needed to more accurately pinpoint why cancer incidence and recurrence is more common in obese children and adults with cancer.
"Our final recommendation in ASCO's clinical practice guideline on chemotherapy dosing for obese adults is the need for more research in pharmacokinetics, and that's true in obese children with cancer as well-maybe even more so in children because of the wide range of weight variation as they go from toddlers to teenagers," saidGary H. Lyman, MD, MPH, Professor of Medicine in the Division of Medical Oncology, Department of Internal Medicine at Duke University School of Medicine and the Duke Cancer Institute, and Co-Chair of ASCO's Guideline Expert Panel.
"As we point out, and studies show," he continued, "obese patients who get dosed based on their actual weight have no greater toxicity and perhaps less than the healthy-weight patient getting full weight-based dosing, and it may be that even with the full calculated dose, they're still getting underdosed pharmacologically. The only way we're going to sort this out is with pharmacokinetics, by looking at the level of drugs in the body, and with pharmacodynamics, by looking at how much of the drug is actually getting to the tumor site."
The recommendations in the new clinical practice guideline, said Dr. Lyman, represent just the first step in providing oncologists with information to help them in their dosing decisions for obese patients. ■
Disclosure:Drs. Lyman and Griggs reported no potential conflicts of interest.
References
1. Butturini AM, Dorey FJ, Lange BJ, et al: Obesity and outcome in pediatric acute lymphoblastic leukemia. J Clin Oncol 25:2063-2069, 2007.
2. Behan JW, Yun JP, Proektor MP, et al: Adipocytes impair leukemia treatment in mice. Cancer Res 69:7867-7874, 2009.
