A phase III trial comparing FULV to FULV + oxaliplatin in stage II or III carcinoma of the colon: Results of the NSABP Protocol C-07.
Reviewer: Christopher Dolinsky, MD
University of Pennsylvania School of Medicine
Last Modified: May 16, 2005
Presenter: N. Wolmark
Presenter's Affiliation: Allegheny General Hospital, Pittsburgh, Pennsylvania
Type of Session: Scientific
- Oxaliplatin is a new chemotherapeutic agent with demonstrated activity in colorectal cancer.
- A previously reported large phase III randomized trial (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.
- The 5-fluorouracil in MOSAIC was given as 24 hour continuous infusion.
- After results of MOSAIC were presented, oncologists wondered if a regimen containing oxaliplatin and bolus 5-fluorouracil would be equally effective.
Materials and Methods
- A multi-institution phase III prospective trial randomized 2492 stage II or III colon cancer patients to either 5-fluorouracil/leukovorin (FULV) or oxaliplatin/5-fluorouracil/leukovorin (FLOX).
- The FULV was given as three, 8 week cycles of 500mg/m2 of 5-FU IV bolus weekly x 6 and 500mg/m2 leukovorin weekly x 6.
- The FLOX was given as oxaliplatin 85mg/m2 on weeks 1, 3 and 5 of each 8 week cycle in addition to the same FULV dosing schedule.
- Patients were stratified by number of positive nodes.
- Primary endpoint was disease free survival.
- The arms were well balanced in terms of age, gender, tumor location and number of nodes.
- 29% of patients were node negative.
- Median follow-up was 34 months.
- 3 year disease free survival was 76.5% in the FLOX arm and 71.6% in the FULV arm.
- The translates into a hazard ratio for the FLOX arm of 0.79, p<0.004 and a 21% risk reduction for this arm.
- Toxicities were well balanced between the arms, with 50% of the FLOX patients developing any grade III/IV toxicity compared to 41% of the FULV patients.
- The worst toxicity in the FLOX arm was neurotoxicity.
- 85% of FLOX patients developed any neurotoxicity during treatment, and 29% of them had any neurotoxicity at 1 year of follow-up.
- 8% of FLOX patients developed grade 3 neurotoxicity during treatment, and 0.5% of them had grade 3 neurotoxicity at 1 year of follow-up.
- 73% of patients received their full planned chemotherapy dose.
- Diarrhea was common in the FLOX arm (40% of patients), although neutropenia was uncommon (4%).
- The addition of oxaliplatin to bolus 5-FU/leukovorin as adjuvant therapy produces a significant improvement in disease free survival for patients with stage II/III colon cancer.
- This trial continues and expands the knowledge about oxaliplatin that was produced from the MOSAIC trial.
- This trial supports the use of oxaliplatin with bolus 5FU/leukovorin.