Results from an abbreviated Phase III randomized trial indicate that Vioxx® (rofecoxib) did not improve survival for Stage II-III colorectal cancer patients when administered following surgery and adjuvant treatment. This study was closed early due to cardiac safety concerns of Vioxx; reported results represent 7.4 months of the intended three to five years of drug exposure. These findings were recently published in the Journal of Clinical Oncology.
Colorectal cancer is the second leading cause of cancer-related deaths in the United States. Although there is no single cause of colon cancer, certain factors increase the risk of developing the disease. These factors include colorectal polyps, a family history of colorectal cancer, and a history of ulcerative colitis. Diet has long been suspected as a contributing factor to the risk of developing colorectal cancer; however, a direct link is presently unclear. Previous research studies have shown that aspirin can decrease the incidence of colon polyps. However, to date no studies have determined the effect of aspirin on established colon cancers.
Vioxx belongs to the class of drugs known as non-steroidal anti-inflammatory agents (NSAIDS). Vioxx inhibits the COX-2 enzyme, which plays a role in inflammation. The COX-2 enzyme is overexpressed in many colorectal cancers, suggesting that inhibitors of this enzyme may play a role in prevention or treatment. Some studies, however, have linked COX-2 inhibitors with an increased risk of cardiovascular problems. Vioxx was withdrawn from the market due to safety concerns over elevated risk of cardiovascular problems associated with long-term use.
In the current Phase III randomized study (initiated before Vioxx was withdrawn from the market), researchers evaluated whether Vioxx could improve survival among patients with Stage II or III colorectal cancer. Eligible patients had undergone surgical removal of their cancer as well as adjuvant treatment. The study was originally designed to include 7,000 patients who would receive either Vioxx or a placebo for three to five years. The study was terminated early due to the withdrawal of Vioxx related to cardiac toxicity concerns. Of the intended 7,000 patients, 2,327 patients were enrolled, and treatment duration was truncated from three to five years to approximately seven months.
Patients treated with Vioxx did not experience a statistically significant improvement in survival or recurrence rate compared with placebo (see Table). In addition, patients whose tumors expressed COX-2 did not appear to experience a benefit from Vioxx versus placebo.
Table: Deaths and Recurrences Reported in Patients Treated with Vioxx Versus Placebo
|Number of patients||Median Treatment Duration, Months||Median Follow-up, years||Deaths||Recurrences|
The researchers concluded that Vioxx given for seven months did not improve survival with Stage II or III colorectal cancer when compared with placebo. Nevertheless, the role of COX-2 inhibitors in colorectal cancer is still being investigated, with safety precautions to minimize cardiovascular complications.