Chemotherapy dosages in overweight or obese patients with ovarian cancer

Ovarian cancer patients who are overweight or obese are often given less chemotherapy per pound of body weight in order to reduce the toxic side effects associated with higher doses, which may lower their chances of survival, according to a study published in JAMA Oncology (doi:10.1001/jamaoncol.2015.1796).

Doses of chemotherapy are generally based on a patient's weight. However, doctors may decide not to provide doses over a certain level to reduce toxic side effects. For patients with cancer who are overweight, this results in reducing the chemotherapy dose per pound of body weight and possibly the effectiveness of chemotherapy in improving outcomes.

“There is a lot of uncertainty in what proper chemotherapy dosing levels should be for overweight and obese patients, based on concerns that using the full dose based on weight or body size could be too toxic,” said lead author Elisa Bandera, MD, PhD, epidemiologist at Rutgers Cancer Institute of New Jersey in New Brunswick, NJ.

“Our study is the first to evaluate the impact of dose reduction in survival after an ovarian cancer diagnosis in normal weight, overweight, and obese women,” said Dr. Bandera. “We found that for each body mass index category, [patients with] ovarian cancer with dose reduction experienced a poorer survival rate.”

Current guidelines issued by the American Society of Clinical Oncology recommend full doses based on actual weight; however, these guidelines were mostly based on studies on patients with breast cancer. This study shows that these guidelines are also appropriate for ovarian cancer, which is the second most common gynecologic cancer and fifth most common in terms of cancer death among women.

This study from the Kaiser Permanente Research on Ovarian Cancer Study cohort included 806 women with epithelial ovarian cancer who received the combination chemotherapy agents paclitaxel and carboplatin. All women studied were diagnosed in Kaiser Permanente Northern California, a region of the nation's largest integrated health care system, and data were obtained from electronic medical records and other clinical and administrative databases.

Approximately 30% of those women studied were obese (BMI of 30 or greater) and 31% were overweight (BMI between 25 and 29); fewer than 3% were underweight (BMI less than 18.5). A high body mass index was the strongest predictor of dose reduction. Researchers found that obese women received less of the chemotherapy drugs paclitaxel and carboplatin per kilogram of body weight and a lower dose intensity when compared to women of normal weight.

Investigators also found that lower dose intensity was associated with a poorer survival rate for patients with ovarian cancer. Women who were obese at diagnosis appeared to have better survival rates, but that advantage disappeared when chemotherapy dosage was reduced.

Regardless of body mass index, those with an average dose reduction of 85% or lower had a 35% higher risk of mortality than those who received normal dosing (85%-100%). This finding was strongest among normal weight women.

“Our observations suggest that body size should not be a principle reason for reducing chemotherapy dose in women with ovarian cancer,” said senior author Lawrence H. Kushi, ScD, epidemiologist at the Kaiser Permanente Northern California Division of Research in Oakland, California.

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