Redefining Adjuvant Therapy for Stage III Resected Colon Cancer
Name of the Trial
Oxaliplatin, Leucovorin Calcium, and Fluorouracil with or without Celecoxib in Treating Patients with Stage III Colon Cancer Previously Treated with Surgery (CALGB-80702). See the protocol summary.
Dr. Jeffrey A. Meyerhardt, Alliance for Clinical Trials in Oncology
Why This Trial Is Important
Despite improvements in treatment, approximately 30 percent of patients with resected (surgically removed) stage III colon cancer still experience a recurrence. Accordingly, clinical trials of new interventions are needed to find better ways of preventing the cancer from returning. In this trial, patients with resected stage III colon cancer are being randomly assigned to receive a type of chemotherapy called FOLFOX for either 3 months or 6 months and to take either an aspirin-like pill called celecoxib (Celebrex®) or a matching placebo pill for 3 years.
"We're really trying to answer two questions with this study: first, does adding celecoxib to chemotherapy following surgery provide any benefit over the chemotherapy alone, and second, does a shorter course of FOLFOX work as well as the standard 6-month course?" said Dr. Meyerhardt, the study's lead investigator.
Resection of the tumor is the cornerstone of treatment for colon cancer that has not spread to other parts of the body. For early-stage disease, surgery alone may be sufficient to eradicate the cancer, but for more advanced stage III colon cancer, the use of chemotherapy after surgery (adjuvant chemotherapy) may help prevent or delay the return of cancer and prolong the lives of patients.
Currently, a 6-month course of adjuvant FOLFOX is considered standard treatment for resected stage III colon cancer. FOLFOX combines fluorouracil and leucovorin, drugs first approved decades ago, with oxaliplatin, a relatively newer platinum-based drug. Clinical trials have demonstrated that this combination extends disease-free survival and overall survival better than adjuvant fluorouracil and leucovorin alone.
Unfortunately, many drugs, including the ones used in this trial, cause side effects. In some cases, these side effects can be severe. One of the most common and serious side effects associated with oxaliplatin is peripheral neuropathy, an often painful "tingling" or numbing sensation in the feet or hands. The likelihood of developing peripheral neuropathy increases with each dose of FOLFOX. This and other side effects can be so severe that patients stop treatment before completing the full 6 months of chemotherapy.
In an effort to limit the toxicity associated with adjuvant FOLFOX, this trial will determine whether a 3-month course of treatment is as good as a 6-month course in delaying or preventing a recurrence of colon cancer. In addition, patients will be monitored to determine whether the shorter course of treatment reduces side effects such as peripheral neuropathy.
This trial also tests celecoxib's ability to help prevent or delay cancer recurrence. Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) that blocks the activity of a protein thought to play a role in cancer growth. A number of large observational studies have shown that people who regularly take aspirin or other NSAIDs may be at reduced risk of developing colon cancer. These findings have led to studies of aspirin and NSAIDs as prevention agents for colon cancer.
The NCI-sponsored Adenoma Prevention with Celecoxib (APC) trial, in particular, tested celecoxib's ability to prevent colon polyps in people who had them removed during a previous colonoscopy and found that the drug did reduce the recurrence of polyps. Most, if not all, cases of colorectal cancer begin as polyps in the colon or rectum. These findings encouraged researchers to test celecoxib as an adjuvant therapy for resected colon cancer.
However, cardiac toxicity is a concern with all NSAIDS, including celecoxib. Previous studies have identified a daily dose of 400 milligrams as the safest dose for celecoxib, and doctors have learned a great deal about which patients are at greater risk of heart complications. This trial is recruiting patients who will be at the least risk for cardiac problems and is using the safest dosage of celecoxib.
"For celecoxib to be incorporated into clinical practice for colon cancer, we need to have a randomized controlled trial to make sure there aren't other factors leading to the associations we’ve observed," said Dr. Meyerhardt.
"We've enrolled 1,700 patients since 2010 and we haven't seen any disturbing trends with either cardiac toxicity or with the shorter course of chemotherapy," he explained. "So we're hopeful that we can reach our goal of 2,500 patients in order to definitively settle these questions."