Long-Term Survival Benefits in Colon Cancer With Oxaliplatin

Barbara Boughton

January 27, 2012

January 27, 2012 (San Francisco, California) — Adjuvant therapy with capecitabine plus oxaliplatin (XELOX) significantly improves overall survival, compared with bolus 5-fluorouracil/leucovorin (5-FU/LV), in patients with resected stage III colon cancer, even 6 to 7 years after the completion of treatment, according to researchers here at the 2012 Gastrointestinal Cancers Symposium.

Oxaliplatin "should now be considered standard treatment for stage III colon cancer," said presenting author Hans-Joachim Schmoll, MD, from the University Clinic Halle (Saale) in Germany.

In this phase 3 randomized trial, 1806 patients with stage III colon cancer underwent adjuvant therapy with either bolus 5-FU/LV or capecitabine plus oxaliplatin.

At a follow-up of 4.75 years, there was a disease-free survival advantage for oxaliplatin over 5-FU/LV (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.69 to 0.93; P = .0045), but the difference in overall survival was not significant.

The latest long-term survival results, with a median follow-up of 6 years, show that the oxaliplatin regimen provided more overall survival benefits than the 5-FU/LV regimen (73% vs 67%; HR, 0.83; P = .0367).

In addition, disease-free survival, the primary end point of the study, was significantly better with oxaliplatin than with 5-FU/LV after a median follow-up of 7 years (63% vs 56%; HR, 0.80; P = .0038).

"Even when we adjusted for prognostic factors such as lymph node status, time from surgery to treatment, and sex and age, the positive treatment effect of [oxaliplatin] remained," Dr. Schmoll announced.

Patients who were older than 70 years benefited less from the oxaliplatin regimen than younger patients, he noted. The trial included a large proportion of patients in this age group — 22% of all enrolled patients, he said.

In fact, in a long-term survival analysis, patients older than 70 years who received oxaliplatin had a hazard ratio of 1. "Although MOSAIC showed that older patients had some improvement with oxaliplatin plus 5-FU/LV, our results in older patients were not clinically significant," Dr. Schmoll said. The MOSAIC trial showed that oxaliplatin plus 5-FU/LV (FOLFOX4) improved 3-year disease-free survival, compared with intravenous and bolus 5-FU/LV as adjuvant therapy in patients with stage II/III colon cancer.

With a median follow-up of 7 years, deaths from colon cancer were 26% in the 5-FU/LV group, compared with 20% in the oxaliplatin group. Oxaliplatin "clearly provides better overall survival and relapse-free survival," Dr. Schmoll said.

"This trial had an acceptable design, but the fact that it included just stage III patients shows us that it's best to be careful about the inclusion of patients with similar stage and molecular subtypes in clinical trials," said Gail Eckhardt, MD, from the University of Colorado at Denver. "This study showed extensive analysis of treatment effects, but toxicity — especially diarrhea and hand–foot syndrome — will be the prime question going forward as we begin to add new agents to this regimen," she noted.

Dr. Eckhardt said researchers need to come up with a better way to measure predictive biomarkers of oxaliplatin response, as well as more data on the optimal duration of therapy. Whether or not 6 months of treatment with oxaliplatin is necessary in colon cancer is being addressed by an ongoing Southwest Oncology Group (SWOG) trial. "The results of that trial should provide us with some answers," she said.

Dr. Schmoll reports being a consultant or advisor to Merck and Roche. Dr. Eckhardt reports being a consultant or advisor to Genentech, Millennium, Onconova, Oncothyreon, and sanofi-aventis.

2012 Gastrointestinal Cancers Symposium (GICS): Abstract 388. Presented January 21, 2012.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.