title: Impact of obesity on chemotherapy dosing for women with advanced stage serous ovarian cancer in the Australian Ovarian Cancer Study (AOCS).
abstract: OBJECTIVE
  Obesity is an increasing health problem that is reported to influence chemotherapy dosing. The extent to which this occurs and whether this affects outcomes in ovarian cancer was unclear. To describe chemotherapy dosing practices in normal, overweight and obese patients treated for FIGO Stage III/IV serous ovarian cancer in the Australian Ovarian Cancer Study (AOCS). To evaluate the relationship between body mass index (BMI), dose intensity of chemotherapy received, overall survival (OS) and progression free survival (PFS).
  
  
  METHODS
  Patient characteristics including age, height, weight, FIGO stage, serum creatinine, primary chemotherapy received and outcome data were extracted from medical records and entered into the AOCS database. Outcomes were analysed against BMI and relative dose intensity (RDI) received, based on calculations derived from a standard regimen (carboplatin AUC 5 and paclitaxel 175mg/m(2)).
  
  
  RESULTS
  333 women were included in the analysis. 27% were overweight and 21% were obese. In cycle 1 66% of obese patients received carboplatin doses more than 5% below their optimal calculated dose, and 32% received sub-optimal paclitaxel doses, compared to 25% and 13% of normal weight patients respectively. Obese women were more likely to have received <85% RDI for carboplatin compared to normal weight women (p<0.001). BMI group and RDI of carboplatin and paclitaxel were not predictors of OS. Women who received less than 85% RDI for carboplatin had a worse PFS (univariate analysis, median PFS 11 versus 15 months; p=0.04). There was no significant association between RDI and OS or PFS in multivariate analysis.
  
  
  CONCLUSIONS
  Obesity is common in ovarian cancer patients, and commonly results in lower chemotherapy dosing than recommended. Analysis of chemotherapy dosing from this study suggests that reduced dose intensity of carboplatin, which was more common in obese women, may impact on PFS in patients with advanced serous ovarian cancer.
authors.affiliation: Department of Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. Electronic address: george.au-yeung@petermac.org.
authors.forename: George
authors.initials: G
authors.lastname: Au-Yeung
authors.affiliation: Gynaecological Cancers Group, QIMR Berghofer Institute of Medical Research, Brisbane, Queensland, Australia.
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Webb
authors.affiliation: Department of Gynaecological Oncology and Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, NSW, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: DeFazio
authors.affiliation: Cancer Genomics Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Sian
authors.initials: S
authors.lastname: Fereday
authors.affiliation: Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Mathias
authors.initials: M
authors.lastname: Bressel
authors.affiliation: Department of Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Linda
authors.initials: L
authors.lastname: Mileshkin
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D015992:Body Mass Index; D016190:Carboplatin / Q000008:administration & dosage*; D002277:Carcinoma / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000150:complications*; D010051:Ovarian Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D050177:Overweight / Q000150:complications; D017239:Paclitaxel / Q000008:administration & dosage*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin; D017239:Paclitaxel
keywords: Chemotherapy dosing; Dose intensity; Obesity; Ovarian cancer; Overall survival; Progression free survival