Rofecoxib and Cardiovascular Adverse Events in Adjuvant Treatment of Colorectal Cancer

• Published in: The New England journal of medicine Vol. 357; no. 4; pp. 360 - 369
• Main Authors: Kerr, David J, Dunn, Janet A, Langman, Michael J, Smith, Justine L, Midgley, Rachel S.J, Stanley, Andrew, Stokes, Joanne C, Julier, Patrick, Iveson, Claire, Duvvuri, Ravi, McConkey, Christopher C
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 26.07.2007
• Subjects: Adenoma - prevention & control; Adenoma - surgery; Aged; Biological and medical sciences; Cancer therapies; Cardiovascular Diseases - chemically induced; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - mortality; Chemotherapy, Adjuvant; Colorectal cancer; Colorectal Neoplasms - prevention & control; Colorectal Neoplasms - surgery; Cyclooxygenase 2 Inhibitors - adverse effects; Cyclooxygenase 2 Inhibitors - therapeutic use; Disease prevention; Drug therapy; Female; Follow-Up Studies; Gastroenterology. Liver. Pancreas. Abdomen; General aspects; Humans; Incidence; Lactones - adverse effects; Lactones - therapeutic use; Male; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - prevention & control; Risk; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Sulfones - adverse effects; Sulfones - therapeutic use; Surgery; Tumors; Prostaglandin-endoperoxide synthase; Rectal disease; Rofecoxib; Enzyme; Toxicity; Colorectal cancer; Adjuvant treatment; Enzyme inhibitor; Cardiovascular disease; Cyclooxygenase 2 inhibitor; Malignant tumor; Colonic disease; Non steroidal antiinflammatory agent; Medicine; Secondary effect; Digestive diseases; Intestinal disease; Complication; Oxidoreductases
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa071841

In this clinical trial, rofecoxib (25 mg per day) was studied in the prevention of recurrent colorectal cancer. Although the median duration of study treatment was only 7.4 months, rofecoxib therapy was associated with an increased risk of cardiovascular adverse events (relative risk as compared with placebo, 2.66; P=0.04). The results indicate that even short-term treatment with rofecoxib may result in cardiovascular toxicity. Rofecoxib therapy was associated with an increased risk of cardiovascular adverse events (relative risk as compared with placebo, 2.66). Approximately half of all patients undergoing potentially curative surgery for colorectal cancer ultimately have a relapse and die of metastatic disease. This has led to the introduction of cytotoxic adjuvant therapy, 1 the benefits of which are relatively small (5 to 10% improvement in the 5-year survival rate). 2 – 4 A range of laboratory investigations suggest that cyclooxygenase-2 (COX-2) plays an important role in colorectal carcinogenesis during the transition from adenoma to carcinoma and subsequently during invasion and metastasis. 5 – 7 Epidemiologic studies have indicated that the incidence of colorectal cancer is reduced by 30 to 70% 8 – 10 in subjects taking nonsteroidal antiinflammatory . . .