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  • Impact of obesity on chemotherapy dosing for women with advanced stage serous ovarian cancer in the Australian Ovarian Cancer Study (AOCS).

Impact of obesity on chemotherapy dosing for women with advanced stage serous ovarian cancer in the Australian Ovarian Cancer Study (AOCS).

Gynecologic oncology (2014-04-01)
George Au-Yeung, Penelope M Webb, Anna DeFazio, Sian Fereday, Mathias Bressel, Linda Mileshkin
ABSTRACT

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). 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)). 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. 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.

MATERIALS
Product Number
Brand
Product Description

Paclitaxel semi-synthetic for peak identification, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Paclitaxel, from Taxus yannanensis, powder
Sigma-Aldrich
Paclitaxel, from semisynthetic, ≥98%
Sigma-Aldrich
Carboplatin
Sigma-Aldrich
Paclitaxel, from Taxus brevifolia, ≥95% (HPLC), powder
Paclitaxel semi-synthetic for system suitability, European Pharmacopoeia (EP) Reference Standard
Paclitaxel, European Pharmacopoeia (EP) Reference Standard
Paclitaxel natural for peak identification, European Pharmacopoeia (EP) Reference Standard