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BMI should not influence chemotherapy dose reductions for ovarian cancer
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Women with ovarian cancer who received paclitaxel and carboplatin dose reductions experienced poorer survival regardless of their body size, according to study results.
However, body size predicted the receipt of chemotherapy dose reductions, results also showed. These results suggest chemotherapy dose reduction for patients with ovarian cancer should not be based on a woman’s body size or their BMI, according to the researchers.
“Our study represents the most comprehensive assessment to date of the impact of dose reduction on ovarian cancer survival, taking into account important prognostic factors,” Elisa V. Bandera, MD, a professor of epidemiology at the Rutgers Cancer Institute of New Jersey, told HemOnc Today. “Despite national guidelines recommending chemotherapy dosing based on full weight, there is considerable variation in dosing practices and uncertainty among oncologists regarding optimal chemotherapy dosing in overweight and obese patients. Because these guidelines were mostly based on breast cancer studies, there is very limited data on ovarian cancer patients. Our study is the first to evaluate these issues specifically in overweight and obese women.”
Elisa V. Bandera
Bandera and colleagues sought to evaluate the association of BMI with chemotherapy dosing — as well as predictors of dose reductions — for patients with ovarian cancer. Researchers also evaluated the efficacy of chemotherapy in improving survival and related toxicities based on BMI.
Researchers used the Kaiser Permanente Northern California Cancer Registry to identify 806 patients with ovarian cancer who were diagnosed between 2000 and 2013 and who received adjuvant first-line carboplatin and paclitaxel with curative intent. Approximately 30% of the population was obese (class 1, 16.6%; class 2, 8.7%; class 3, 4.6%) and 30.8% were overweight.
BMI and dose intensity
Overall, the strongest predictor of dose reduction was a high BMI. A dose reduction — defined as a relative dose intensity (RDI) of less than 85% — was significantly more common among women with a BMI of at least 35 for both paclitaxel (P = .01) and carboplatin (P < .001).
Further, there was a significant inverse association between BMI and the total dose of the chemotherapy drugs administered per kilogram of body weight. When compared with women of normal weight, obese class 3 women received a 38% lower dose of paclitaxel and a 45% lower dose of carboplatin (P < .001 for both).
BMI and the average RDI for the initial cycle of treatment as well as all cycles combined also were inversely correlated. The mean average RDI for the treatment for all cycles was 73.7% for obese class 3 women compared with 88.2% for women of normal weight (P < .001).
When compared to normal-weight women, obese women were more likely to receive a dose reduction. The OR for a dose reduction in average RDI was 2.85 (95% CI, 1.79-4.55) for obese class 1 women and 19.85 (95% CI, 7.21-54.65) for obese class 3 women.
An average RDI less than 70% increased the risk for overall mortality (HR = 1.62; 95% CI, 1.1-2.37) and ovarian cancer-specific mortality (HR = 1.69; 95% CI, 1.12-2.55) compared with an average RDI between 85% and 100%.
Multivariable-adjusted analyses that considered joint effects of BMI and average RDI indicated normal-weight women who received a dose reduction (average RDI ˂ 85%) experienced worse survival compared with normal-weight women who did not receive dose reductions (HR = 1.5; 95% CI, 1.02-2.21).
Women who received an average RDI of less than 85% had worse survival compared with women who did not receive dose reductions in every BMI category. Although results of analyses adjusted for prognostic factors indicated women who were obese at diagnosis had improved survival, this survival advantage no longer persisted when women received dose reductions.
“We found that dose reduction was associated with poorer outcomes in each BMI category, although a stronger association was found for normal-weight women,” Bandera said. “Our findings suggest that body size should not be a deciding factor on chemotherapy dosing decisions. These results provide important information to clinicians for the management of ovarian cancer. Further research is needed to understand the impact of dose reduction after longer follow-up time, as well as the role of obesity and weight changes (post-diagnosis weight loss and weight gain) in ovarian cancer prognosis in general.”
Remaining questions
The study data indicate that overweight and obesity are nearly as common among women with ovarian cancer as in the general population.
“Over 60% of ovarian cancer patients are overweight or obese, with even much higher prevalence in certain populations, such as African American women, and therefore, these issues are very important in the management of ovarian cancer,” Bandera said.
Still, these data pose more questions for researchers, particularly with regard to the definition of body size, S. Percy Ivy, MD, associate chief of the investigational drug branch in the cancer therapy evaluation program in the division of cancer treatment and diagnosis at the NCI, and Jan H. Beumer, PharmD, PhD, an associate professor of pharmaceutical sciences in the school of pharmacy at University of Pittsburgh, wrote in an accompanying editorial.
“The reader is left to struggle with the conundrum of dosing based on [body size area], whether to use lean body mass or actual weight in the Cockroft-Gault formula and whether dose capping still has a place,” they wrote. “How to resolve these issues in an evidence-based fashion is challenging. Clearly treatment outcome is closely related to RDI for a number of drugs, but not all drugs are created equal. Decisions on dosing considering size remain both an art and a science until definitive data are generated.” – by Anthony SanFilippo
For more information:
Elisa V. Bandera MD, can be reached at the Rutgers Cancer Institute of New Jersey, 195 Little Albany St., New Brunswick, NJ, 08901; email: elisa.bandera@rutgers.edu
Disclosure: This study was funded by the NCI and the Kaiser Permanente Center for Effectiveness and Safety Research. The researchers report no relevant financial disclosures.
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