DO NOT UNDERDOSE DRUGS IN OVERWEIGHT WOMEN WITH OVARIAN CANCER

NEW YORK (Reuters Health) - Although body surface area (BSA) has been used to calculate dosage for some chemotherapy drugs for more than 40 years, and it's common to reduce doses for obese patients for fear of toxicity, the authors of a new research paper say don't base dosage on body size.

"Our study provides additional evidence that chemotherapy dose reduction is associated with worse cancer survival. While decisions should be tailored to each patient, based on comorbidities, age, etc., capping the dose merely on the basis of large body size does not seem to be justified," Dr. Elise V. Bandera, of the Rutgers Cancer Institute of New Jersey in New Brunswick, told Reuters Health by email.

Dr. Bandera and colleagues analyzed data on 806 ovarian cancer patients in the Kaiser Permanente Northern California integrated health care system receiving first-line carboplatin and paclitaxel between 2000 and 2013.

The median duration of follow-up was 52.5 months, according to a report online July 2 in JAMA Oncology.

Body mass index (BMI) was the strongest predictor of dose reduction. Women with a class 3 BMI (at least 40) received lower relative dose intensity (RDI) for each drug than normal-weight women. Also, lower RDI independently predicted ovarian cancer mortality.

Women who were obese class 3 received 38% less paclitaxel and 45% less carboplatin per kg of body weight than normal-weight women (p<0 .001="" 3="" 73.7="" 88.2="" and="" average="" came="" class="" compared="" for="" mean="" normal-weight="" obese="" p="" rdi="" the="" to="" with="" women="">

The researchers found lower average RDI to be associated with worse overall and ovarian cancer-specific survival (hazard ratio 1.62 and 1.69, respectively).

They also found that compared with women with normal weight and no dose reduction, normal-weight women with dose reduction had worse survival (HR 1.50).

In each of the three BMI categories - normal, overweight, or obese - women whose average RDI fell below 85% had worse survival than women who did not have dose reduction.

"We were surprised that the impact of dose reduction was more apparent in normal-weight women than obese women, even after adjusting for major prognostic variables and comorbidities and toxicities. This finding needs further exploration with longer follow-up time," Dr. Bandera said.

She concluded, "Based on our findings and the recommendations of the American Society of Clinical Oncology, physicians should not cap the dose just because the patient is obese. More research is needed to better understand the impact of dose reduction in normal-weight and obese patients, and possible reasons for reduced mortality."

"Our findings need to be replicated by other studies," Dr. Bandera added. "Also, our findings may not be generalizable to other drugs beyond carboplatin and paclitaxel. We based our study in those two because it is the most common regimen in ovarian cancer treatment, and because the dosing of these two drugs is based on weight/body size."

Dr. S. Percy Ivy, of the National Cancer Institute, Bethesda, Maryland, and Dr. Jan H. Beumer, of the University of Pittsburgh Cancer Institute in Pennsylvania, who cowrote an accompanying editorial, agree.

"Collection of well annotated data is important to address the issue of dosing chemotherapeutics in patients with a range of demographic variables such as BSA and BMI, and these questions need to be asked for each and every drug individually," they told Reuters Health in a joint email.

But they don't think practice will change soon. "Without more evidence, physicians are unlikely to change their behavior. More databases and analyses such as the one reported here are required to build a critical mass of evidence for every drug," they said. "The presence of this database is a great resource, and with some more information collected, there are many more questions that may be answered."

The National Cancer Institute and the Kaiser Permanente Center for Effectiveness and Safety Research funded this study. The authors reported no disclosures.

SOURCE: http://bit.ly/1LLb0ut

JAMA Oncol 2015.