Failure to Follow Weight-Based Chemo Guidelines Lowers Survival in Ovarian Cancer

Elisa Bandera, MD, PhD

Women with ovarian cancer who experienced an average dose reduction of ≤85% had a 35% higher mortality risk than those who received normal dosing (85%-100%). The dose reductions were more likely to occur in overweight or obese patients, according to findings from a study published online in JAMA Oncology.

“Our study is the first to evaluate the impact of dose reduction on survival after an ovarian cancer diagnosis in normal weight, overweight, and obese women,” said lead study author Elisa Bandera, MD, PhD, epidemiologist at the Rutgers Cancer Institute of New Jersey, in a statement. “We found that for each body mass index category, ovarian cancer patients with dose reduction experienced a poorer survival rate.”

In a cohort study, investigators with the Rutgers Cancer Institute of New Jersey and the Kaiser Permanente Northern California (KPNC) Division of Research evaluated data from 806 women at KPNC receiving first-line treatment for their epithelial ovarian cancer with adjuvant carboplatin and paclitaxel. Data were obtained from electronic medical records and the KPNC Mortality Linkage System.

The median patient follow-up time was 52.5 months. Primary outcome measures included overall and ovarian cancer—related mortality.

Across the study, 30%, 31%, and 3% of patients, respectively, were categorized as obese (BMI ≥30), overweight (BMI = 25-29), and underweight (BMI <18.5). Compared with women of normal weight, obese women received less paclitaxel and carboplatin per kilogram of body weight and lower dose intensity.

Overall, lower dose intensity yielded worse outcomes—regardless of BMI&mdash;and was an independent predictor of ovarian cancer mortality. Researchers noted that the effect of dose reduction was actually strongest among normal-weight women, and this finding held true even after accounting for such diagnostic and prognostic factors as posttreatment CA-125 levels, disease stage, and comorbid conditions.

High BMI was the strongest predictor of dose reduction. Women who were obese class III (BMI ≥40) received 38% lower doses in mg/kg of paclitaxel and 45% lower doses of carboplatin, compared with normal-weight women. For these women, the mean average relative dose intensity (ARDI) was 73.7% compared with 88.2% for their normal-weight counterparts.

An ARDI of <70% was linked to worse overall survival (HR = 1.62; 95% CI, 1.10-2.37) and ovarian cancer—specific survival (HR = 1.69; 95% CI, 1.12-2.55). Although women who were obese at diagnosis appeared to have better survival rates, that advantage disappeared when their chemotherapy dose was reduced.

Chemotherapy dosing is generally based on a patient’s weight. However, dosing levels can vary considerably, in part because providers opt not to provide doses over a certain level due to worries over increased toxicity. 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.

The study authors noted that much of the data on chemotherapy dosing—upon which the ASCO expert panel—derived guidelines are based&mdash;are drawn from breast cancer research, and less is known about chemotherapy dosing in patients with ovarian cancer who are overweight or obese. They hope that their cohort analysis will now offer some guidance in this area.

“Our observations suggest that body size should not be a principal reason for reducing chemotherapy dose in women with ovarian cancer,” noted senior author Lawrence H. Kushi, ScD, epidemiologist at the KPNC Division of Research, in a statement. The authors concluded that, “neither survival nor toxicity is worse when obese women are given full drug doses of chemotherapy.”

Bandera EV, Lee VS, Rodriguez-Rodriguez L, et al. Impact of chemotherapy dosing on ovarian cancer survival according to body mass index [published online July 2, 2015]. JAMA Oncol. doi: 10.1001/jamaoncol.2015.1926.