Predictors of reduced relative dose intensity and its relationship to mortality in women receiving multi-agent chemotherapy for epithelial ovarian cancer

Abstract

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Objective

There is limited information concerning the role of relative dose intensity (RDI) on clinical outcomes in solid tumors. The objectives of our study were to evaluate the prognostic significance of RDI and predictors of reduced RDI in women with newly diagnosed advanced stage epithelial ovarian carcinoma (EOC) treated with platinum-based chemotherapy.

Methods

A multi-center retrospective study of women with FIGO stage III–IV epithelial ovarian cancer treated postoperatively with multi-agent intravenous chemotherapy between 1995 and 2009 was conducted. Data were obtained to include the first four chemotherapy cycles administered. Outcomes included: (1) planned and delivered relative dose intensity (RDI), (2) progression-free (PFS) and overall (OS) survival. Survival estimates were based on Kaplan and Meier method, and multivariate analyses were based on logistic regression and Cox proportional hazards regression.

Results

Evaluable subjects included 325 women. With median follow-up of 34 months (range, 0.4–170), progression or recurrence was recorded in 241 (73.9%) and death in 179 (54.9%). In multivariate analysis, predictors of reduced planned RDI were: treatment off research protocols (odds ratio [OR] = 4.3; P < 0.001) and BSA > 2 m² (OR = 6.14; P < 0.001); predictors of reduced delivered RDI were: BMI over 30 kg/m² (OR = 2.35; P = 0.008) and use of carboplatin (OR = 2.71; P = 0.008). In multivariate analysis, the following factors were independently associated with OS: delivered RDI < 85% (hazard ratio [HR] = 1.71; P = 0.003) and elevated CA-125 at cycle 1 (HR = 2.29; P = 0.017).

Conclusion

In this retrospective analysis, reduced chemotherapy RDI for ovarian cancer was associated with lower OS, but not PFS, despite adjustment for established prognostic factors.

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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.