Impact of obesity on chemotherapy dosing for women with advanced stage serous ovarian cancer in the Australian Ovarian Cancer Study (AOCS)
Introduction
Epithelial ovarian cancer (EOC) is the second most common gynaecological malignancy diagnosed in Australia and other Western populations, and is responsible for the most deaths due to gynaecological malignancies [1]. Initial treatment includes cytoreductive surgery followed by platinum-based chemotherapy, generally resulting in excellent response rates. However 5 year overall survival rates remain poor largely due to advanced stage of most cancers at presentation and the development of recurrent disease [2].
The incidence of obesity is increasing in the Western population. Studies have shown that 30% of EOC patients are overweight, and 12% are obese [3]. There are conflicting reports on the effect of obesity on EOC survival. Some studies indicate that obesity is a negative prognostic factor, whilst others do not demonstrate a significant impact [4], [5], [6], [7]. A recent study of 1391 patients analysing data collected as part of the Australian Ovarian Cancer Study (AOCS) suggested that women with EOC who are obese have worse survival compared to non-obese women after adjusting for known prognostic factors [8]. However, other studies in Asian and North American populations failed to demonstrate any significant association between obesity and clinical outcomes in EOC [5], [6], [7]. In a recently published meta-analysis of 14 studies, obese women had a hazard ratio for survival of 1.17 (95% CI 1.03–1.034) compared to non-obese women [9].
Obesity has been shown to affect chemotherapy dosing among women with breast cancer, with significant variability in prescribing practices reported [10], [11]. This is largely due to the concerns of clinicians regarding the potential for over-dosing and chemotherapy associated toxicities [12]. In particular, calculations of body surface area (BSA) and measurements of renal function that are used to determine chemotherapy doses often vary among clinicians, suggesting a high degree of uncertainty regarding optimal dosing in this population. Use of ideal body weight rather than actual body weight, and capping the BSA at 2.0 m2 are strategies that are commonly utilised by clinicians when treating obese patients [12]. This may negatively influence clinical outcomes, with multiple studies particularly in breast cancer highlighting the relationship between accurate chemotherapy doses for body size and treatment efficacy, particularly in a curative setting [13], [14], [15], [16].
It is likely that similar issues may exist in the management of EOC outside of clinical trials. This study aimed to describe the chemotherapy dosing strategies in EOC, utilising data collected as part of AOCS, a large collaborative population study. We also evaluated the relationship between body mass index (BMI) and total percentage of intended chemotherapy dose received, overall survival (OS) and progression free survival (PFS).
Section snippets
Study design
This is a retrospective study of patients previously enrolled in AOCS. AOCS is a prospective population-based study that recruited women aged 18–79 years newly diagnosed with primary epithelial ovarian cancer (including fallopian tube and primary peritoneal cancers) between 2002 and 2006. Women were recruited through major treatment centres and state-based cancer-registries across Australia. AOCS collected detailed epidemiological data, pathology and initial treatment data, as well as ongoing
Results
620 patients in the AOCS cohort had Stage III/IV disease treated with carboplatin-based chemotherapy and thus were eligible for this analysis. Of these, 287 were excluded because complete records of height, weight or serum creatinine levels were not available. These patients were compared to the 333 patients included in the analysis and were found to be similar in terms of age, stage and residual disease (all p > 0.05, data not shown), demonstrating that the study population was representative of
Discussion
We aimed to review chemotherapy dosing practices in a population study of advanced EOC patients treated outside of a clinical trial setting. The patient characteristics of our study cohort were similar to those reported in the literature. Five year OS was approximately 40% across all BMI groups. 27% of patients were overweight and 20% were obese, similar to previous reports [3], [6], [7].
Conflict of interest statement
The authors declare no relevant conflicts of interest.
Acknowledgements
We would like to thank all the women and institutions who participated in the Australian Ovarian Cancer Study. Full membership of the AOCS Group is listed at http://www.aocstudy.org/.
AOCS was supported by the U.S. Army Medical Research and Material Command under DAMD-17-01-1-0729, the Cancer Council Victoria, Queensland Cancer Fund, The Cancer Council New South Wales, The Cancer Council South Australia, the Cancer Foundation of Western Australia, The Cancer Council Tasmania and the National
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