CHAPEL HILL, NC - In an editorial in the October 20, 2010 issue of the Journal of Clinical Oncology, UNC’s Richard Goldberg, MD, and Harvard’s Monica Bertagnolli, MD, examine the medical field’s track record of clinical trials for patients who have undergone colon cancer surgery.
The topic has been controversial, as selective COX-2 inhibitors such as rofecoxib (marketed as Vioxx) have been withdrawn from the market due to evidence of increased cardiovascular risk.
Goldberg and Bertagnolli argue that the benefit of COX-2 inhibitors for high-risk colon cancer patients can outweigh the potential cardiovascular risk for multiple reasons.
The COX-2 enzyme is known to be an early, critical factor that drives multiple physiological factors that lead to tumor development in adenomas and colon cancers. Previous studies have demonstrated that treatment with drugs that inhibit COX-2 can decrease the recurrence of colon adenomas between 20 and 25 percent, depending on the dosage administered. While some increased cardiovascular risk was observed, these adverse events were most common in patients who already had a history of cardiovascular disease.
In addition, these patients are much more likely to die of colon cancer or its complications than of adverse cardiovascular events caused by COX-2 inhibitors, which are known to be much less toxic than standard chemotherapy agents commonly used to treat stage III colon cancer.
The authors note: “One could argue that the frequency and severity of adverse events in a trial onto which people with cancer are enrolled, who have a high risk for recurrence and subsequent death as a result of their illness, should differ from that which is reasonable in a prevention trial.”
A new trial initiated by the Cancer and Leukemia Group B (CALGB)/Southwest Oncology Group (SWOG), opened this summer and will provide evidence to more definitively state whether COX-2 inhibitors combined with standard treatment are more effective than standard treatment alone. Goldberg and Bertagnolli argue that, by excluding patients with a history of cardiovascular disease and testing a dose and frequency of COX-2 inhibitors that has been shown to have a lower risk, this new trial will provide important evidence that may significantly benefit colon cancer patients in the future.
Richard M. Goldberg, MD, is division chief of the division of hematology/oncology at the UNC-Chapel Hill School of Medicine, Physician-in-Chief of the N.C. Cancer Hospital and Associate Director for Clinical Research at the UNC Lineberger Comprehensive Cancer Center. He serves as Associate Group Chair for Intergroup Affairs at CALGB.