Colorectal Cancer Clinical Trials
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Accomplishments of the NSABP in Colorectal Cancer

The NSABP began its research program in colorectal cancer in 1977, and since that time has randomized almost 15,000 patients into large Phase III trials. The data from these trials have had a significant influence on the treatment of colorectal cancer and, indeed, a trial initiated in 1987 established chemotherapy as the standard of care following surgical removal of the primary tumor in colon cancer patients (NSABP C-04). A review of the findings after ten years of follow-up of these patients still shows a substantial survival advantage in favor of 5-FU and leucovorin, the backbone of regimens still used today. Because of the positive result from this early trial, 5-FU and leucovorin was used as the control arm for subsequent NSABP trials assessing adjuvant therapy in patients with colon cancer. A study that accrued nearly 2,500 patients was reported at the 2005 meeting of ASCO (NSABP C-07), the largest international oncology meeting in the world. The study demonstrated the value of adding a third drug (oxaliplatin) to the standard of 5-FU and leucovorin, which produced a significant improvement in disease-free survival.

The NSABP has also contributed to the advancement of adjuvant therapy for patients with rectal cancer. A controlled clinical trial demonstrated a significant improvement in local tumor control when pelvic radiation therapy was given in addition to postoperative chemotherapy. This is an important finding since uncontrolled tumor in the pelvis can produce severe pain, infections, and interference with function of the urinary bladder. Another clinical trial demonstrated that radiation and chemotherapy can be safely given preoperatively for patients with rectal cancer, and that the achievement of a complete tumor response correlates with improved long term outcome.

The NSABP is presently conducting a study to determine if the addition of anti-angiogenesis therapy with bevacizumab, a new genetically engineered monoclonal antibody that “starves” the tumor by interrupting the blood supply, will increase the effectiveness of chemotherapy treatments currently used to treat patients with colon cancer in the surgical adjuvant setting.

In rectal cancer, the NSABP is conducting a clinical trial to improve the effectiveness and convenience of preoperative chemotherapy when combined with radiation for operable rectal cancer. The oral agent capecitabine is being evaluated to determine if it can be substituted for continuous infusion 5-FU, a cumbersome treatment that requires central venous catheters and ambulatory infusion pumps. It will also determine whether the addition of oxaliplatin to the chemotherapy regimen will further improve local tumor control. Hopefully, fewer patients will require radical surgical resection of the rectum with establishment of a permanent colostomy when treated with the newer regimens. The NSABP will also collaborate with another cooperative group to determine the value of bevacizumab combined with chemotherapy following rectal cancer surgery to prevent tumor relapse.

The goal of these trials is to conduct definitive Phase III multidisciplinary surgical adjuvant studies to improve the long-term survival of patients with cancer of the colon or rectum.

The NSABP is also committed to help tailor treatments for inpidual patients through study of molecular tumor markers. In collaboration with Genomic Health, Inc., a molecular assay (RT-PCR) has been applied to paraffin-embedded tumor specimens from patients participating in NSABP colon cancer adjuvant therapy clinical trials over the years. Preliminary results indicate the possibility of selecting which colon cancer patients truly need postoperative chemotherapy following removal of their colon cancer, and which are very likely cured with surgery alone. If confirmed by other studies in progress, these results will spare many patients now receiving adjuvant chemotherapy the risk and side effects associated with these treatments. Other tumor marker studies are addressing which patients have an excellent chance of cure when treated with standard 5-FU and leucovorin chemotherapy, and which would be best served by incorporation of newer systemic agents. The overall goal of these studies is to identify which patients require further treatment following surgery and which regimen would be most effective for each patient.

Of great importance to all cancer patients, is the improvement of the quality of their lives and to that end, the NSABP was one of the first research groups to establish quality of life studies as an integral part of our major Phase III trials. The NCI and others have long looked to the NSABP for leadership in this vital area of research. In the area of rectal cancer, our goal is to improve the efficacy and decrease the toxicity of the pre-operative chemotherapy and radiation therapy treatment required of these patients. The primary goal is to increase the number of patients who can undergo sphincter-sparing surgery, thereby avoiding the need for a colostomy. In moving toward our ultimate goal of cure and our immediate goal of long-term survival, we must seriously consider the quality of life that new treatment measures can provide.

Over the last several years, accrual to our Phase III breast and colorectal trials has increased significantly. Indeed, when comparing our most recent 5 year grant period with the previous 5 years, there was a 100% increase in the number of patients accrued to our studies, and the number of accruals per institution increased 161%. During this period, we reduced the number of sites by instituting several requirements resulting in greater efficiency, higher accruals, increased data integrity, and lower costs.

As the NSABP moves into its 51st year, we are positioned to maintain our leadership in cancer research. Our goal remains the same: to identify targeted treatment and prevention regimes; ultimately, leading to cure and prevention strategies in breast and bowel cancer.