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Rofecoxib ineffective as adjuvant treatment for colorectal cancer

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – Rofecoxib used as adjuvant therapy does not improve survival or reduce recurrences in patients who have undergone surgery for colorectal cancer, according to final results of the abbreviated Vioxx in Colorectal Cancer Therapy: Definition of Optimal Regime (VICTOR) trial published in the Journal of Clinical Oncology online September 13.

Cyclooxygenase (COX)-2 plays an important role in colorectal carcinogenesis, including invasion, angiogenesis, and metastasis, note Dr. Rachel S. Midgley at the University of Oxford, UK, and colleagues.

Along with previous research showing that aspirin (another COX-2 inhibitor) reduced colorectal cancer risk in tumors overexpressing COX-2, this information led the investigators to hypothesize that rofecoxib would provide a safe approach to blocking COX-2 and reduce the rate of tumor recurrence in patients who had undergone potentially curative surgery for colorectal cancer.

The VICTOR trial compared overall survival and disease-free survival among 1217 such patients randomly assigned to rofecoxib and 1217 similar patients assigned to placebo. The population actually treated consisted of 1167 rofecoxib patients and 1160 placebo patients, because the trial was terminated when rofecoxib was withdrawn from the market. At that point, patients had been treated for a median of about 8 months.

After a median follow-up of about 58 months in both groups, there were 241 deaths in the rofecoxib group and 246 in the placebo group, with an overall 3-year Kaplan-Meier survival rate of 87.7% for the rofecoxib group and 86.9% for the placebo group.

Overall survival and colorectal cancer-specific mortality did not differ between the rofecoxib and placebo groups.

Three-year disease-free survival rates were also similar for the rofecoxib group (75.6%) and for the placebo group (73.4%), although there were significantly more recurrences in the first year in the placebo group (141 recurrences) than in the rofecoxib group (110 recurrences)(p=0.044).

There was little evidence to support an association between the degree of tumor COX-2 expression and prognosis.

“The present study was compromised by the worldwide withdrawal of rofecoxib and, therefore, significant reduction in the duration of exposure for patients who were randomly assigned,” the researchers point out. “However, there is still significant interest in the potential role of COX-2 inhibition in cancer secondary prevention, and a further trial of this family of drugs with careful patient selection, maintenance of exposure, and a careful parallel assessment of biomarkers is worthy of consideration.”

“Indeed,” they add, “a Cancer and Leukemia Group B/Southwest Oncology Group phase III trial that is about to open will test celecoxib in a 2 X 2 factorial fashion with infusional fluorouracil, leucovorin, and oxaliplatin (3 months versus 6 months of therapy) in the adjuvant setting of colorectal cancer.”


Phase III Randomized Trial Assessing Rofecoxib in the Adjuvant Setting of Colorectal Cancer: Final Results of the VICTOR Trial

J Clin Oncol 2010.