Analysis of prognostic factors for 60-day mortality: Evaluation of a randomized phase III trial investigating FUFIRI versus mIROX as first-line treatment of metastatic colorectal cancer (mCRC).

Abstract

3554 Background: Mortality rates in published irinotecan-based randomized trials range between 1.7% and 5.0%. Prognostic factors for death within the first 60 days of treatment in mCRC studies have not been published yet. The purpose of this analysis was to evaluate clinical, histopathological and lab-report data associated with PFS and OS as published by Koehne et al. (Annals of Oncology 13: 308, 2002) and to identify prognostic factors of 60-day mortality in pts receiving first-line therapy of mCRC. Methods: Data from a randomized phase III study comparing FUFIRI vs. mIROX in 479 pts were evaluated. According to Koehne et al. we analyzed: Platelets, alkaline phosphatase (AP), white blood cell count (WBC), haemoglobin, number of tumor sites, LDH, CEA, CA 19-9 and several other baseline parameters. Prognostic factors were estimated via uni- and multivariate logistic regression analysis. Apart from Karnofsky performance status (KPS), none of these factors were part of the in- or exclusion-criteria in the FIRE trial. Results: The total 60-day mortality rate was 5.0% (24/479). 60- day mortality was observed in 5.5% (13/238) of pts in the FUFIRI-arm and in 4.6% (11/241) in the mIROX-arm (p = 0.680). Mortality was qualified as disease-related in 71% (17 pts) and treatment-related in 29% (7 pts) (p = 0.695). Univariate analysis showed KPS, LDH, AP and WBC as prognostic factors for death within first 60 days of treatment. In multivariate analysis, only high LDH-levels (p = 0.010) and an elevated WBC (p = 0.006) remained as significant, independent prognostic factors. Low KPS showed a strong trend, but failed to reach statistical significance (p = 0.057) as did AP and the number of metastatic sites. Conclusions: In this study, 71% of early deaths were disease-related, while only 29% were possibly related to study medication. Independent prognostic factors for death within the first 60 days of treatment were LDH and WBC. KPS showed a strong trend in multivariate analysis. Future trials may consider LDH and WBC for definition of exclusion criteria. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis