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.
Promising Results
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.
Side Effects
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.
Looking Ahead
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.