Meta-analysis Comparing Cisplatin Total Dose Intensity and Survival

Abstract

Objective: To determine the relationship between total dose intensity (TDI) of cisplatin/carboplatin, total dose intensity of all chemotherapy drugs (GDI) and median survival (MS) in stage III-IV ovarian cancer patients. Methods: Over 700 studies from the English literature were reviewed. Prospective clinical trials that had at least one arm treating patients with cisplatin/carboplatin and provided data on both MS and dose and schedule of chemotherapy were included. Dose intensity (DI), TDI, and GDI were calculated for each study arm. To explore possible relationships, several linear regression models were fitted with MS as the dependent variable and DI, TDI, GDI, and other known prognostic factors as the independent variables. Results: Sixty-one study arms were analyzed including 4118 patients. No significant correlation was found between DI and TDI of cisplatin and MS ( P = 0.90 and P = 0.11 respectively). Of the 10 variables tested, proportion of patients optimally debulked (%OD), proportion of mucinous tumor, and GDI were found to have a significant correlation to MS. All studies with a GDI less than 20 and %OD < 20 had a MS less than 20 months. On the other hand 77% of studies have a MS greater than 20 months when GDI is >20 and %OD > 20%. We found single-agent chemotherapy had the worst outcome and there was very little difference between two or more drugs for percentage of studies with >20 months MS, (56.5% vs 63.3% respectively). Conclusions: From this meta-analysis we believe that both GDI and %OD are important factors that determine outcome in terms of median survival.