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Colorectal Cancer

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NEW YORK-Patients with advanced colorectal cancer have a median survival of only 12 months with single-agent chemotherapy. New drugs and new drug combinations are being tested in an attempt to find more effective treatments for the disease. A panel of researchers discussed trials of raltitrexed (Tomudex) in combination with other drugs at the Chemotherapy Foundation Symposium XVII.

Preliminary clinical data presented at a poster session of the 1999 annual meeting of the American Society of Clinical Oncology (ASCO) revealed that a significant number of patients with advanced colorectal cancer respond to first-line treatment with raltitrexed (Tomudex) in combination with oxaliplatin. The response rate of 59% suggests that this regimen may be one of the more active combinations under current investigation for the disease.

NEW YORK-A new oral combination chemotherapy regimen is as effective as intravenous fluorouracil (5-FU) and leucovorin, the current treatment standard, but with a superior safety profile. Speaking at the Chemotherapy Foundation Symposium XVII, Paulo Hoff, MD, assistant professor of medicine, M.D. Anderson Cancer Center, described the use of an oral regimen combining uracil/tegafur (UFT) and leucovorin as first-line treatment of metastatic colorectal cancer.

NEW YORK-The folate antagonist trimetrexate (TMTX) may be useful as a biochemical modulator of fluorouracil (5-FU) in the treatment of advanced colorectal cancer, according to preliminary results of a phase III trial conducted by the European TMTX Study Group and discussed at the Chemotherapy Foundation Symposium XVII

BUFFALO, NY-Colorectal cancer is caused by a multistep process, taking up to 25 years for an adenocarcinoma to develop. This offers multiple opportunities for prevention strategies to intervene and decrease the incidence of this disease.

BETHESDA, Md-G.D. Searle & Co. has won FDA approval for its COX-2 inhibitor Celebrex (celecoxib) as an oral adjunct to usual care (endoscopic surveillance and surgery) to reduce the number of adenomatous colorectal polyps in patients with familial adenomatous polyposis (FAP). The FDA initially approved Celebrex for treating osteoarthritis and rheumatoid arthritis in April 1998.

Researchers have identified a mechanism that may explain where colorectal tumors arise and at what age the tumors develop in people with hereditary nonpolyposis colorectal cancer (HNPCC). The results of the study, conducted at Ohio State’s Comprehensive Cancer Center, help clarify why some people with the same HNPCC-related genetic mutation develop colorectal tumors at 30 years of age while others develop tumors at age 60. They also help explain why tumors in some patients develop in the distal area of the large intestine rather than in regions closer to the large intestine’s junction with the small intestine, which is more typical.

Aphase III clinical trial conducted by researchers at Lehigh Valley Hospital, Allentown, Pennsylvania, found that the OncoVAX colon cancer vaccine reduced the 5-year recurrence rate of patients with stage II colon cancer patients by 61% and improved their cancer-free survival rate by 50%. The study, published in a recent issue of the Lancet, compared patients who underwent surgery alone to patients who had surgery plus the vaccine.

PHOENIX-Conservative, sphincter-sparing surgery followed by chemotherapy plus radiotherapy appears effective in selected patients with early-stage rectal cancer, Anthony Russell, MD, said at the American Society for Therapeutic Radiology and Oncology meeting.

Colorectal cancer is a major cause of death in the United States, where it accounts for approximately 57,000 deaths per year. Thus, the prevention of this disease would have a significant impact on public health. Chemoprevention is defined as the use of natural or pharmacologic agents to disrupt the process of carcinogenesis. Substances explored as chemopreventive agents in colorectal cancer include: (1) the nonsteroidal anti-inflamma-tory drugs (NSAIDS), which may inhibit the evolution and formation of adenomas by their inhibition of cyclooxygenase and decrease of prostaglandin synthesis; (2) antioxidants, such as vitamin E or C, which may modulate carcinogenic substances; and (3) folate and calcium, which may interfere with tumor cell growth and replication. Dietary intervention can be accomplished by decreasing fat intake and increasing fiber consumption, both of which have been linked to a lower incidence of colon cancer in multiple epidemiologic studies. This field is continuing to evolve. Hopefully, ongoing research efforts will offer a better understanding of the role of these and other substances in chemoprevention. This article summarizes the available data regarding dietary and pharmacologic approaches to colorectal cancer chemoprevention. [ONCOLOGY 1(13):89-98, 1999]