Chemotherapy Dose Reductions Yield Worse Survival in Women With Ovarian Cancer

Findings of a new study show that failure to follow professional practice guidelines for weight-based chemotherapy dosing can lead to poorer survival in women with ovarian cancer.

Elisa Bandera, MD, PhD

Findings of a new study show that failure to follow professional practice guidelines for weight-based chemotherapy dosing can lead to poorer survival in women with ovarian cancer.

The study, published online in JAMA Oncology, found that patients who experienced an average dose reduction of ≤85% had a 35% higher risk of mortality than those who received normal (85% to 100%) dosing. Women who were overweight or obese were more likely to have their chemotherapy doses 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 idea that we are under dosing a large population of our sickest patients should give pause to all of us," said Emily Beard, RN, OCN, CBCN, coordinator of Women's Oncology Program at Northside Hospital Cancer Institute. "Obesity rates are increasing in this country right along with cancer rates, so the thought of putting patients through the toxicity and morbidity of treatment only to have them not achieve their therapeutic goal is an issue of quality and ethics, and an area that begs for more evidence and guideline development to better guide our actions."

Study authors noted that much of the data on chemotherapy dosing—upon which the American Society of Clinical Oncology expert panel—derived guidelines are based—are drawn from breast cancer research, and less is known about chemotherapy dosing in patients with ovarian cancer who are overweight or obese.

"As with everything in the current oncology care continuum, I think the answer lies in our multidisciplinary approach to care. It takes the entire team—oncologist, pharmacist, infusion nurse, dietician (just to name a few) working together—to evaluate how a patient’s weight and overall metabolic status affects their treatment," Beard said.

Investigators with the Rutgers Cancer Institute of New Jersey and the Kaiser Permanente Northern California (KPNC) Division of Research sought to shed light on this question through a cohort study involving 806 women at KPNC receiving first-line treatment for their epithelial ovarian cancer with adjuvant carboplatin and paclitaxel.

Emily Beard, RN, OCN, CBCN

Primary study outcomes were overall and ovarian cancer—related mortality, and patients were followed for a median of 52.5 months. Data were gleaned from electronic medical records and the KPNC Mortality Linkage System.

Approximately 30% of participants were obese (BMI ≥30), and 31% were overweight (BMI = 25-29); fewer than 3% were underweight (BMI less than 18.5). Researchers found that obese women received less paclitaxel and carboplatin per kilogram of body weight and lower dose intensity when compared with women of normal weight.

Overall, lower dose intensity yielded worse outcomes—regardless of BMI—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 CA125 levels, disease stage, and comorbid conditions.

“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.”

High BMI was the strongest predictor of dose reduction. Women who were obese class III (BMI ≥40) received 38% lower doses in milligrams per kilogram 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 (hazard ratio [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.

“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.