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

https://doi.org/10.1016/j.ygyno.2014.01.030Get rights and content

Highlights

  • Obesity is common among patients with advanced serous ovarian cancer, and significant variability exists in chemotherapy dosing.

  • Obese women with advanced serous ovarian cancer were more likely to receive under-dosing and a reduced dose intensity.

  • Women who received less than 85% relative dose intensity of carboplatin had a worse progression free survival.

Abstract

Objectives

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 175 mg/m2).

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.

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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