Body mass index impacts ovarian cancer chemotherapy dosages

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, and this in turn may lower their chances of survival, according to a study by researchers at the Rutgers Cancer Institute of New Jersey and the Kaiser Permanente Northern California Division of Research. The study was published in the online edition of JAMA Oncology.

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 real and serious toxic side effects. For cancer patients 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 Elisa Bandera, MD, PhD, epidemiologist at Rutgers Cancer Institute of New Jersey and lead author of the study.

"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, who is also a professor of epidemiology at Rutgers Robert Wood Johnson Medical School and Rutgers School of Public Health. "We found that for each body mass index category, ovarian cancer patients 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 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 percent of those women studied were obese (BMI of 30 or greater) and 31 percent were overweight (BMI between 25 and 29); fewer than three percent 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 - that is, a lower dose than expected - when compared to women of normal weight.

Investigators also found that lower dose intensity was associated with a poorer survival rate for ovarian cancer patients. 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 percent or lower had a 35 percent higher risk of mortality than those who received normal dosing (85 percent to 100 percent). This finding was strongest among normal weight women.

"Our observations suggest that body size should not be a principal 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.

Kaiser Permanente has the largest private patient-centered electronic health system in the world, which connects Kaiser Permanente research scientists and their collaborators to one of the most extensive collections of longitudinal medical data available. "This study demonstrates the potential for electronic medical records to examine questions of clinical importance," Dr. Kushi said.

Along with Bandera and Kushi, co-authors were Valerie S. Lee, MHS, Kaiser Permanente Division of Research; Lorna Rodriguez, MD, PhD, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School; and C. Bethan Powell, MD, Kaiser Permanente Northern California, San Francisco.

This study was supported by grants from the National Cancer Institute (K22 CA138563, UC2 CA148185, U24 CA171524) and the Kaiser Permanente Center for Effectiveness and Safety Research.