Effective management of patients receiving XELOX: Evaluation of impact of dose modifications on outcome in patients from the NO16966, NO16967, and NO16968 trials.

Abstract

497 Background: In patients (pts) with metastatic colorectal cancer (MCRC), XELOX is non-inferior to FOLFOX4 in terms of PFS and OS as either first-line (NO16966, Cassidy et al. JCO 2008) or second-line therapy (NO16967, Rothenberg et al. Ann Oncol 2008). In pts with stage III colon cancer (NO16968, Haller et al. ECCO-ESMO 2009), adjuvant XELOX is superior to 5-FU/LV in terms of DFS. While XELOX is generally well tolerated, regional differences in fluoropyrimidine tolerability were noted in a pooled analysis [Rothenberg et al. ASCO GI 2008], leading to use of lower than recommended doses of capecitabine (i.e. 1,000mg/m2 bid d1–15 with oxaliplatin 130mg/m2 d1 q3w) in some countries. Methods: NO16966, NO16967 and NO16968 protocols included standard dose/schedule modifications for capecitabine, 5-FU and oxaliplatin for treatment-related adverse events (AEs). Safety parameters included AEs, deaths, laboratory parameters, exposure to trial medication, and withdrawals. In NO16966 and NO16967, Kaplan-Meier curves for PFS were developed for pts with no treatment modifications, and pts with dose reductions, treatment interruptions or cycle delays to assess the effect of treatment modifications on efficacy. NO16968 also included a planned analysis of the effect of dose modifications on DFS. Results: NO16966 included 1335 pts with previously untreated MCRC receiving XELOX or FOLFOX4. NO16967 included 627 pts with previously treated MCRC receiving XELOX or FOLFOX4. NO16968 included 1886 pts with resected stage III disease receiving XELOX or 5-FU/LV; dose modifications were required for capecitabine in 65% and oxaliplatin in 62% of pts in NO16968. Kaplan-Meier curves of PFS (NO16966/NO16967) or DFS (NO16968) for pts who did and did not require dose modifications indicated that the efficacy of XELOX did not appear to be compromised by dose modifications. Indeed, pts who required dose modifications seemed to have a favourable outcome compared with those who did not. Conclusions: From these data we cannot make a recommendation that initial dosing should be lower than the labeled dose. However, it is clear that dose modification does not seem to impact patient outcome. [Table: see text]