title: Impact of Chemotherapy Dosing on Ovarian Cancer Survival According to Body Mass Index.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: Cancer Prevention and Control, Rutgers Cancer Institute of New Jersey, New Brunswick2Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick.
authors.forename: Elisa V
authors.initials: EV
authors.lastname: Bandera
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland.
authors.forename: Valerie S
authors.initials: VS
authors.lastname: Lee
authors.affiliation: Precision Medicine, Division of Gynecologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick.
authors.forename: Lorna
authors.initials: L
authors.lastname: Rodriguez-Rodriguez
authors.affiliation: Gynecologic Oncology, Kaiser Permanente Northern California, San Francisco.
authors.forename: C Bethan
authors.initials: CB
authors.lastname: Powell
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland6Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis School of Medicine, Sacramento.
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Kushi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D015992:Body Mass Index; D002140:California; D000077216:Carcinoma, Ovarian Epithelial; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D002945:Cisplatin / Q000008:administration & dosage*; D054796:Drug Dosage Calculations; D006279:Health Maintenance Organizations; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009765:Obesity / Q000150:complications* / Q000175:diagnosis / Q000401:mortality; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage*; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D017239:Paclitaxel; D002945:Cisplatin