Body mass index should not be a major determinant of whether women with ovarian cancer receive reduced-dose chemotherapy, investigators say.
Because body surface area calculations are used to determine the dose of paclitaxel in the standard paclitaxel and carboplatin regimen for ovarian cancer, some centers treat obese women with reduced doses, in the belief that dose reduction can provide clinical benefit while minimizing toxicity. Normal-weight women may also have dose reductions when they experience serious adverse events following early cycles of chemotherapy.
But those dose reductions may be compromising survival, caution Dr. Elisa V. Bandera from the Robert Wood Johnson Medical School in New Brunswick, N.J., and her colleagues. They found that in a cohort of 806 obese and normal-weight women with epithelial ovarian cancer receiving first-line paclitaxel and carboplatin with curative intent, women with class 3 obesity (body mass index >40 kg/mg2) received 38% lower doses of paclitaxel, and 45% lower doses of carboplatin than did normal-weight women, and also received lower relative dose intensity (RDI) than did normal-weight women for each agent separately and for the combination regimen.
The mean average RDI was 73.7% for women in obese class 3, compared with 88.2% for normal-weight women (P < .001). Average RDI lower than 70% was associated with both worse overall survival (OS; hazard ratio, 1.62; 95% confidence interval, 1.10-2.37) and worse ovarian cancer-specific survival (HR, 1.69; 95% CI, 1.12-2.55), the investigators report (JAMA Oncology 2015 July 2 [doi: 10.1001/jamaoncol.2015.1796]).
Although women who were obese at diagnosis appeared to have better survival than normal-weight women did in an analysis adjusted for prognostic factors, that survival advantage disappeared with dose reduction.
In a multivariable analysis looking at the joint effects of BMI and average RDI, the authors found that normal-weight women who received less than 85% of the standard dose had a 1.5-fold higher risk for mortality than did similar women who did not have dose reduction. For each category of BMI, patients who had average RDI less than 85% of normal had worse survival than did similar-sized patients with no dose-reductions.
“In this study we found that obese patients with ovarian cancer received considerably less paclitaxel and carboplatin/kg of body weight and lower RDI for each chemotherapy agent and for the combined regimen. We also found that the strongest predictor of dose reduction, defined as an RDI below 85%, was a high BMI. Dose reduction was associated with reduced survival time, particularly for normal-weight women. This association was apparent even after accounting for diagnostic and prognostic factors such as stage of disease, comorbid conditions, or posttreatment CA125 levels, a marker of residual disease,” they write.