Oxaliplatin in Combination with a Bolus 5-Fluorouracil/Leucovorin Regimen Reduces Recurrence in Early Stage Colon Cancer

Multiple randomized trials over the last three decades have validated the use of systemic therapy to prolong survival for patients with stage III colon cancer. In one recent study, the CCOP sponsored MOSAIC, a large, randomized clinical trial, which demonstrated that oxaliplatin, when combined with infusional 5-fluoro-uracil (5-FU) and leucovorin (LV), increased the three-year disease-free survival (DFS) for patients with early-stage colon cancer compared to standard therapy 5-FU/LV alone. The MOSAIC trial, however, did not address whether oxaliplatin in combination with bolus 5-FU and LV, a less burdensome treatment regimen, would lead to the same improvement in three-year DFS.

Following MOSAIC, CTEP sponsored a trial known as NSABP C-07, which was a randomized prospective study designed to determine whether bolus 5-FU/LV plus oxaliplatin (FLOX) would increase three-year DFS compared to a bolus schedule of 5-FU/LV alone.

More than 2400 patients with early-stage colon cancer were randomized to receive either bolus 5-FU/LV or FLOX. The primary endpoint was DFS. Events were defined as first recurrence, second primary cancer, or death. The median follow-up for patients who were still alive was 34 months. Three-year DFS was 76.5 percent for the group of patients who received FLOX and 71.6 percent for the group who received bolus 5-FU/LV.

The addition of oxaliplatin to weekly bolus 5-FU/LV significantly improved three-year DFS in patients with stage II and III colon cancer. The NSABP C-07 trial confirmed and extended the results of the MOSAIC trial by demonstrating that oxaliplatin in combination with a bolus schedule of 5-FU/LV resulted in a similar benefit for patients with early-stage colon cancer.

Wolmark N, Wieand HS, Kuebler JP, Colangelo L, Smith RE. A phase III trial comparing FULV to FULV + oxaliplatin in stage II or III carcinoma of the colon: results of NSABP Protocol C-07. Proc Am Soc Clin Oncol 2005:23;246S.