Impact of Chemotherapy Dosing on Ovarian Cancer Survival According to Body Mass Index

Abstract

IMPORTANCE Optimal chemotherapy dosing in obese patients remains uncertain, with variation in practice. Dose reduction strategies are often used to avoid chemotoxicity, but recent American Society of Clinical Oncology guidelines recommend full dose. OBJECTIVE To evaluate the impact of body mass index (BMI) on chemotherapy dosing and of dose reduction on ovarian cancer survival. DESIGN, SETTING, AND PARTICIPANTS Cohort study in Kaiser Permanente Northern California (KPNC) health care setting of patients with primary invasive epithelial ovarian cancers diagnosed from January 2000 through March 2013. Analyses focused on 806 patients receiving adjuvant first-line therapy of carboplatin and paclitaxel with curative intent. MAIN OUTCOMES AND MEASURES Overall and ovarian cancer–specific mortality. Deaths were identified through the KPNC Mortality Linkage System, with median follow-up of 52.5 months. Hazard ratios (HRs) and 95% CIs were estimated from proportional hazards regression, accounting for prognostic variables including age at diagnosis, race, stage, grade, histologic type, chemotoxic effects, comorbidities, cancer antigen 125 levels, and BMI at diagnosis. RESULTS The strongest predictor of dose reduction was a high BMI. Compared with normal-weight women, obese class III women received 38% and 45% lower doses in milligrams per kilogram of body weight of paclitaxel and carboplatin, respectively (P < .001 for each agent). They also received lower relative dose intensity (RDI) for each agent and the combined regimen, calculated as average RDI (ARDI). Mean ARDI was 73.7% for obese class III women and 88.2% for normal-weight women (P < .001). Lower ARDI (<70%) was associated with worse overall (HR, 1.62 [95% CI, 1.10–2.37]) and ovarian cancer–specific survival (HR, 1.69 [95% CI, 1.12–2.55]). Women who were obese at diagnosis appeared to have better survival. In multivariable-adjusted analyses considering joint effects by BMI and ARDI, compared with women with normal weight and no dose reduction, normal-weight women with dose reduction (ARDI < 85%) experienced worse survival (HR, 1.50 [95% CI, 1.02–2.21]). For each BMI category, those with ARDI less than 85% had worse survival than those without dose reduction. The improved survival among obese women was no longer apparent with dose reduction. CONCLUSIONS AND RELEVANCE Lower RDI was an independent predictor of ovarian cancer mortality. This finding was strongest among normal-weight women but seen at all levels of BMI. Our results suggest that body size should not be a major factor influencing dose reduction decisions in women with ovarian cancer.

Muscle mass at the time of diagnosis of nonmetastatic colon cancer and early discontinuation of chemotherapy, delays, and dose reductions on adjuvant FOLFOX: The C‐SCANS study

“…To distinguish clinically-significant treatment delays, we counted each instance over the course of therapy that the patient received chemotherapy ≥3 days later than the guidelines-recommended 2 week gap between administrations and dichotomized this at ≥3 instances of treatment delay. Per prior publications, 17 we computed relative dose intensity (RDI) over the course of therapy actually received, as the delivered dose intensity (total dose in mg/m 2 actually administered divided by the time in weeks to complete chemotherapy) divided by expected dose intensity based on the planned course of treatment (first administered dose in mg/m 2 , divided by 24 weeks, the standard time to complete 12 cycles of FOLFOX). We defined “dose reductions” as RDI<0.70, a standard cut-point used in the oncology literature.…”

Racial/Ethnic Disparities in Ovarian Cancer Treatment and Survival

“…The Kaiser Permanente-Research on Ovarian Cancer Survival (KP-ROCS) Cohort Study has been described in detail elsewhere 6 . In brief, cases of invasive epithelial ovarian cancer 21 years or older and diagnosed from 2000-2013 were identified through the KPNC Cancer Registry.…”

“…These differences have been attributed to unequal access to care and receipt of treatment 3 . AA women are also more likely to be obese and to have related comorbidities 4, 5 , which are known to affect chemotherapy dosing, and dose reduction has been shown to reduce ovarian cancer survival 6 . Previous studies have not taken these factors into account, and possible disparities among other racial/ethnic groups have received little attention.…”

Prognostic implications of reproductive and lifestyle factors in ovarian cancer

“…This is likely due to concerns that the heaviest women would not receive optimal chemotherapeutic dosing due to dose limits set in the context of normal or underweight [47,48]. Several reviews, meta-analyses, and pooled analyses of existing studies have been conducted [49][50][51][52][53].…”