Impact of Chemotherapy Dosing on XXXX Survival According to Body Mass Index.

@entity1 @entity43 @entity28 @entity3003 @entity1311 @entity204
Importance: Optimal chemotherapy dosing in @entity28 @entity1 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 @entity43 survival. Design, Setting, and @entity1 : Cohort study in Kaiser Permanente Northern California (KPNC) health care setting of @entity1 with primary @entity43 diagnosed from January 2000 through March 2013. Analyses focused on 806 @entity1 receiving adjuvant first-line therapy of @entity3003 and @entity1311 with curative intent. Main Outcomes and Measures: Overall and @entity43 -specific mortality. @entity204 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 @entity1 , @entity28 class III @entity1 received 38% and 45% lower doses in milligrams per kilogram of body weight of @entity1311 and @entity3003 , 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 @entity28 class III @entity1 and 88.2% for normal-weight @entity1 (P   <   .001). Lower ARDI (<70%) was associated with worse overall (HR, 1.62 [95% CI, 1.10-2.37]) and @entity43 -specific survival (HR, 1.69 [95% CI, 1.12-2.55]). @entity1 who were @entity28 at diagnosis appeared to have better survival. In multivariable-adjusted analyses considering joint effects by BMI and ARDI, compared with @entity1 with normal weight and no dose reduction, normal-weight @entity1 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 @entity28 @entity1 was no longer apparent with dose reduction. Conclusions and Relevance: Lower RDI was an independent predictor of @entity43 mortality. This finding was strongest among normal-weight @entity1 but seen at all levels of BMI. Our results suggest that body size should not be a major factor influencing dose reduction decisions in @entity1 with @entity43 .
