For Best Survival in Ovarian Cancer, Chemotherapy Doses Must be in Line with Body Weight

According to professional practice guidelines, women with ovarian cancer should get doses of chemotherapy that are based on their weight. When they receive less than that, a new study has found, the result can be poorer survival.

The study, published online in JAMA Oncology, found that patients who got 85 percent or less of the chemotherapy they needed based on their weight had a 35 percent higher risk of death than those who received 85 to 100 percent of the recommended dose. 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 a reduction in the chemotherapy dose per pound of body weight — and possibly a reduction in the effectiveness of chemotherapy when it comes to improving outcomes.

Much of the data on chemotherapy dosing — which formed the basis for guidelines written by an expert panel of the American Society of Clinical Oncology — are drawn from breast cancer research, and less is known about chemotherapy dosing in patients with ovarian cancer who are overweight or obese.

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 with epithelial ovarian cancer receiving adjuvant first-line treatment with carboplatin and paclitaxel.

Primary study endpoints 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 percent of participants were obese (BMI [body mass index] of 30 or more), and 31 percent were overweight (BMI of 25-29); fewer than 3 percent 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 to 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 post-treatment levels of cancer antigen 125 (CA125), a protein in the blood that may indicate the presence of ovarian cancer, as well as 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, epidemiologist at 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 3 (BMI of 40 or greater) received 38 percent lower doses in milligrams per kilogram of paclitaxel and 45 percent lower doses of carboplatin, compared with normal-weight women. For these women, the mean average relative dose intensity (ARDI) was 73.7 percent compared with 88.2 percent for their normal-weight counterparts.

An ARDI of less than 70 percent was linked to a 62 percent worse overall survival rate and a 69 percent worse ovarian cancer—specific mortality. 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, 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.”