New York, NY, September 28, 2000 -- In an international study published today in the New England Journal of Medicine, researchers at Memorial Sloan-Kettering Cancer Center report the development of a new chemotherapy regimen for first line treatment for patients with metastatic (widespread) colorectal cancer. This disease is the second leading cause of cancer death, with an estimated 56,300 men and women expected to die this year in the United States alone. The study showed patients receiving the new regimen had improved tumor response rates and improved overall survival as compared to those on standard treatment.
The combination therapy, developed by Dr. Leonard B. Saltz and colleagues at Memorial Sloan-Kettering, consists of irinotecan (also known as CPT-11 or Camptosar®) along with the standard drugs, fluorouracil (5FU) and leucovorin. For decades, the standard therapy for metastatic colorectal cancer has been the drug 5FU, usually given with a vitamin called leucovorin (LV). Irinotecan is a newer agent that was approved by the Food and Drug Administration in 1996 as a second-line treatment for use after 5FU-based treatment had failed. It works by blocking a protein known as Topoisomerase I (Topo I), an important enzyme that allows DNA to unwind so that the cancer cell can divide.
Starting in 1994, Dr. Saltz and colleagues began working on a way to give both 5FU/LV and irinotecan at the same time for initial therapy. Now a large randomized clinical trial shows that this new combination of irinotecan, 5FU, and LV nearly doubled the tumor response rate as compared with 5FU/LV alone. Perhaps more importantly, the median survival of patients receiving the combination was longer, with the relative risk of death at any time on study reduced by 20 percent as compared to the old therapy.
"This combination is the most effective treatment we have now for patients with advanced colorectal cancer," said Dr. Saltz, a medical oncologist who specializes in gastrointestinal tumors. "In the multi-center trial, we saw an improvement in response rate, in time to disease progression, and in survival, with no resulting detriment to quality of life. Most importantly, the combination showed some ability to benefit virtually all subgroups of patients including males, females, the elderly, younger patients, vigorous people, or those less active."
In the trial, 683 patients with metastatic colorectal cancer were randomly assigned to receive either the then standard treatment of 5FU and LV (231 patients), the irinotecan/5FU/LV combination (226 patients), or irinotecan alone (226 patients) as initial therapy. While irinotecan alone showed no benefit over 5FU/LV, the combination of irinotecan/5FU/LV therapy was superior to the old standard 5FU/LV in all endpoints reviewed. The progression-free survival was 7.0 months compared to 4.3 months. The confirmed tumor response rate was 39 percent versus 21 percent, and the overall survival median was 14.8 months compared to 12.6 months. The incidence of serious side effects was not increased with the new combination. Although there was somewhat more diarrhea and nausea with the newer regimen, there was less of a decline in the white blood cell count (and therefore less vulnerability to serious infections), and less irritation of the mucous membranes. Pharmacia, Inc., the company ! ! that has overseen the development of irinotecan in North America, supported the study.
"These results are exciting not only because of what this treatment can offer right now to our most advanced patients," said Dr. Saltz, "but also because this combination may be able to improve the cure rate when used in the post-operative setting for patients with earlier stage colon cancer."
To that end, Dr. Saltz is leading a North American-wide study through the National Cancer Institute's intergroup consortium comparing this schedule of irinotecan/5FU/LV to 5FU/LV alone for patients with earlier stage (stage III) colon cancer. These patients have had their tumor removed by surgery but are still at risk for recurrence.
Memorial Sloan-Kettering Cancer Center is the world's oldest and largest institution devoted to prevention, patient care, research, and education in cancer. Throughout its long and distinguished history, the Center has played a leadership role in defining the standards of care for patients with cancer.
Journal
New England Journal of Medicine