In patients with Dukes C colorectal cancer, therapy with a novel murine monoclonal antibody, Mab 17-1A (edrecolomab [Panorex]), manufactured by Centocor, reduced death by 32% and recurrence of disease by more than 23%, according to a study published in the May 1998 issue of the Journal of Clinical Oncology. These results were maintained for 7 years.
"This study validates the long-term benefit of treatment with Mab 17-1A in patients with Dukes C colorectal cancer," said Gert Riethmuller, MD, of the Institute of Immunology in Munich, Germany, and lead author of this study.
The study evaluated 189 patients from six medical centers throughout Germany who were followed for a median of 7 years. The primary end points of this outcome study were survival and the period of time patients remained free of cancer. Patients in the trial had adenocarcinoma of the colon or rectum that had spread to regional lymph nodes.
Surgery was required to remove cancerous tumors before patients were randomized to one of two treatment arms: observation only or an infusion of 900 mg of Mab 17-1A (with 500 mg given postoperatively, followed by four monthly doses of 100 mg). An observation arm was appropriate, as the role of chemotherapy following surgery had not been established when the study started.
After 7 years, only 39 (43%) of 90 patients who received Mab 17-1A had died, as compared with 48 (63%) of 76 patients in the observation group. In addition, the intent-to-treat analysis showed a significant effect of the monoclonal antibody on overall survival. The survival benefit observed is comparable to data reported from studies of standard chemotherapy regimens. Recurrence of tumor was noted in 47 (52%) of 90 patients who received Mab 17-1A vs 49 (64%) of 76 untreated patients. Of the total 189 patients, 23 could not be evaluated for response.
In this clinical study, Mab 17-1A was generally well tolerated by most patients. The most commonly reported adverse events were malaise, low-grade fevers and chills, and mild-to-moderate gastrointestinal reactions. Side effects observed with treatment of Mab 17-1A compare favorably with the more serious side effects associated with chemotherapy.
Dukes C colorectal cancer is one of the most common types of cancer in the industrialized world and, despite current therapies, remains one of the most common causes of cancer deaths. According to recent estimates, there are 380,000 cases of colorectal cancer diagnosed each year in the United States and Europe and 40,000 new cases reported in Germany.
Mab 17-1A has been available in Germany for the treatment of Dukes C colorectal cancer since December 1994. It is not approved for sale in the United States or other countries.
Four phase III clinical trials in the United States and Europe are currently underway, and the first results should be available in the year 2000. Trials in North and South America are evaluating Mab 17-1A as an addition to standard chemotherapy in newly resected Dukes C colon cancer and as single agent in Dukes B2 colon carcinoma. In Europe and the rest of the world, Mab 17-1A is being evaluated both as a single agent and in addition to standard chemotherapy in newly resected Dukes C colon cancer. Mab 17-1A is also being studied in combination with radiation and chemotherapy in Dukes B and C rectal cancer.
"These results with Mab 17-1A are evidence of the potential therapeutic benefit of monoclonal antibodies," said Richard McCloskey, md, chief medical officer,
Centocor. "The number of patients and the length of follow-up in the phase III trials are large enough to detect significant effects on clinically important end points, such as death and survival free of cancer."
More information can be found on Centocors home-page at www.centocor.com.