Oxaliplatin-Based Chemotherapy for Colon Cancer

For more than 40 years the treatment of colorectal cancer was based upon the use of 5-fluoruracil (5-FU) administered according to a variety of schedules, either alone or with several modulators. The response rate ranged between 10% and 20% with progress ion-free survival (PFS) of 6 months and overall survival of around I year. The introduction into the clinic of oxaliplatin, a diaminocyclohexane platinum analogue, and the demonstrated synergistic activity when combined with 5-FU, led to the popular scheme FOLFOX 4 and its simplified forms, including more recent evolutions with capecitabine as a substitute for leucovorin-modulated 5-FU. We learned from several randomised phase III trials that in the advanced setting these combinations could produce a response rate ranging from 37 to 50% with a progression-free survival of around 8-9 months. Furthermore, a small percentage of unselected patients initially considered inoperable may become resectable following chemotherapy. Oxaliplatin-based regimens can be further strengthened by the addition of a third component, either a traditional drug such as CPT11 or a targeted agent such as the anti VEGF antibody bevacizumab and the anti-EGFR receptor cetaximab. The sequential administration of all these active agents significantly improved the outcome of advanced colorectal cancer patients with several studies reporting median survivals exceeding 20 months. Two large phase III studies (the MOSAIC trial and the NSABP C07) enrolling patients with stage 11 and III colon cancer have consistently demonstrated a 5% absolute improvement in a 3-year DFS favouring the oxaliplatin-containing arms. In the MOSAIC trial the improved 3-year DFS translates in a statistically significant better 6-year survival only for stage III patients (73% vs. 68.6%).