Predictors of reduced relative dose intensity and its relationship to mortality in women receiving multi-agent chemotherapy for epithelial ovarian cancer☆
Highlights
► Relative dose intensity (RDI) is calculated as delivered dose intensity divided by a literature-derived standard dose intensity. ► In this retrospective analysis, RDI less than 85% of standard was associated with lower overall survival. ► Calculation and reporting of RDI in future prospective trials would be informative to further investigate these findings.
Introduction
Relative dose intensity (RDI), defined as the amount of a chemotherapeutic agent delivered compared to a standard dosing schedule over a specific time frame, has been implicated as a prognostic factor in several cancers. The relationship of response rates to RDI was introduced by Hryniuk and Bush, who observed a steep linear relationship between higher actual delivered chemotherapy RDI and improved response rates in metastatic breast cancer trials [1]. Strong evidence also exists in the lymphoma literature showing that RDI reductions are associated with lower survival [2]. In ovarian cancer, multiple trials have failed to demonstrate a survival advantage to escalating the dose intensity of primary chemotherapy [3], [4], [5], [6], [7], [8], [9], [10], [11]. However, only one prior study has specifically addressed the concept of RDI in ovarian cancer; Repetto et al. reported that RDI reductions had no impact on response rates or survival in patients with primary ovarian cancer after surgical management [12].
The aim of the current study was to evaluate factors predictive of (1) reduced RDI and (2) progression free survival (PFS) and overall survival (OS) in women with advanced stage epithelial ovarian carcinoma receiving their initial course of intravenous multi-agent chemotherapy following surgery.
Section snippets
Methods
This is a retrospective multi-center study of women who underwent primary surgical cytoreduction of International Federation of Gynecology and Obstetrics (FIGO) stage III–IV epithelial ovarian cancer at the University of North Carolina Hospitals (UNC) or Duke University Medical Center (DUMC) during the calendar years 1995 through 2009. Eligible patients were identified via ovarian tumor registries at both institutions. Institutional Review Board approval was obtained at each institution.
Results
Three hundred twenty five subjects met inclusion criteria, of whom 124 received primary treatment at UNC and 201 at DUMC. Table 2 shows the demographics. The median age at diagnosis was 60 years (range 24–84 years). One hundred eight patients (33.2%) had no comorbidities recorded, 187 (57.5%) had 1 or 2 comorbidities, and 30 (9.2%) had 3 or more comorbidities. More than two thirds of subjects (69.5%) had a BMI of less than 30 kg/m2 while 20.6% were obese or morbidly obese. Ninety percent (n = 291)
Discussion
While multiple previous studies have failed to identify an advantage to escalating the dose intensity of chemotherapy for ovarian cancer [3], [4], [5], [6], [7], [8], [9], [10], [11], the role of maintaining relative dose intensity in comparison to defined standard dosing regimens is not yet well defined. In this retrospective analysis of 325 women with advanced stage ovarian cancer, we found that maintenance of relative dose intensity of chemotherapy was associated with improved overall (OS),
Conflict of interest statement
Rabbie K. Hanna, Robin A. Laskey, Micael A. Lopez, Aaron Shafer, Laura J. Havrilesky, Robin A. Laskey, Linda Van Le, Marek S. Poniewierski, and Paola A. Gehrig, declare no conflict of interest. Gary H. Lyman, Angeles Alvarez Secord, and David C. Dale have received research funding from Amgen not related to the current study.
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2023, Cancer Treatment and Research CommunicationsCitation Excerpt :A study by Au-Yeung et al. in patients with advance stage serous ovarian cancer treated with carboplatin, found obese (BMI > 30.0 kg/m2 patients to receive significantly more often a dose reduction of RDI < 85% compared with non-obese patients [34]. Furthermore, a study by Hanna et al. in patients with epithelial ovarian cancer treated with carboplatin found that a BMI > 30.0 kg/m2 was a strong and significant predictor for a lower RDI (OR = 2.35, 95%-CI: 1.25 -4.41) [35]. A study by Bandera et al. investigating the effect of BMI on carboplatin chemotherapy dosing in ovarian cancer found high BMI being the strongest predictor for dose reduction [36].
Antineoplastic dosing in overweight and obese cancer patients: an Associazione Italiana Oncologia Medica (AIOM)/Associazione Medici Diabetologi (AMD)/Società Italiana Endocrinologia (SIE)/Società Italiana Farmacologia (SIF) multidisciplinary consensus position paper
2021, ESMO OpenCitation Excerpt :Additionally, a benefit of a higher chemotherapy dose was described by the Cancer and Leukemia Group B (CALGB) study 8541 and the French Adjuvant Breast Cancer Group,55,56 suggesting the existence of a strong correlation between treatment dose and outcome in early breast cancer patients, in terms of disease-free survival and overall survival (OS), regardless of body weight. Chemotherapy dose reduction and treatment delays have also been shown to negatively impact on OS in metastatic breast, ovarian and lung cancer settings.57-61 Chemotherapy dose capping nevertheless often occurs in clinical practice, particularly among overweight and obese patients, in order to avoid toxicities.
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Presented at the 47th Annual Meeting of the American Society of Clinical Oncology, June 4–7, 2011, Chicago, IL.