Oxaliplatin/5FU/LV in the adjuvant treatment of stage II and stage III colon cancer: Efficacy results with a median follow-up of 4 years.

Reviewer: Christopher Dolinsky, MD
University of Pennsylvania School of Medicine
Last Modified: May 16, 2005

Presenter: A. deGramont
Presenter's Affiliation: Hopital Saint Antoine, Paris, France
Type of Session: Scientific

Background

Oxaliplatin is a new chemotherapeutic agent with demonstrated activity in colorectal cancer.
This abstract presents an update to previously published results from a large phase III randomized trial (MOSAIC).
MOSAIC demonstrated superiority of a regimen containing oxaliplatin/5- fluorouracil/leukovorin (FOLFOX4) to one containing 5-fluorouracil and leukovorin (LV5FU2) as adjuvant therapy for stage II and III colon cancer (Andre et al., NEJM 2004).

Materials and Methods

A multi-institution phase III prospective trial randomized 2246 patients with stage II/III colon cancer to either FOLFOX4 or LV5FU2 given as adjuvant therapy.
Both regimens were given every 2 weeks for 6 cycles.
40% of patients were stage II and 60% of patients were stage III.
Primary endpoint was disease free survival.
Median follow-up was 56.2 months, and all patients had minimum follow-up of 4 years.

Results

The FOLFOX4 arm had improved disease free survival compared to the LV5FU2 arm at 4 years median follow-up (hazard ratio 0.77, p<0.001).
This improvement held up for both stage II patients (hazard ratio 0.82) and stage III patients (hazard ratio 0.75)
Grade 3 or 4 neutropenia was seen in 41% of the FOLFOX4 patients, and 4.7% of the LV5FU2 patients.
12.4% of the FOLFOX4 patients developed grade III neurotoxicity, although it resolved completely in 80% of these patients.
There was no significant difference in overall survival between the two arms (84.9% FOLFOX4 arm vs. 82.8% LV5FU2 arm).

Author's Conclusions

The disease free survival benefit seen after 4 years of median follow-up was amplified and confirmed with this data.
Follow-up is ongoing, and a statistically significant difference in overall survival may eventually be realized.
Late recovery from sensory neuropathy is present and common.

Clinical/Scientific Implications

This was a well designed and well executed large phase III trial. The results of this trial confirm oxaliplatin's safety and efficacy as adjuvant therapy for stage II/III colon cancer. The FOLFOX4 regimen has become the standard of care in many communities, and this update should further cement the importance of this regimen. The data from MOSAIC are fairly mature, although it will be interesting to see if the overall survival curves end up diverging in the future. It appears that higher stage patients have a greater magnitude of benefit from this regimen, and further well performed subset analyses should be enlightening. The success of this regimen has sparked a large body of research, and ongoing work using FOLFOX4 in combination with targeted therapies may continue to improve outcomes in this disease.