NEW YORKA monoclonal antibody (MoAb) is being studied as
monotherapy and in combination with standard fluorouracil (5-FU) in
two large phase III trials of stage III colon cancer. The drug is
edrecolomab (Panorex), a murine IgG2a MoAb that recognizes the 17-1A
antigen, which is preferentially expressed on adenocarcinomas.
Alan M. Keller, MD, co-director of clinical research, US Oncology,
Tulsa, Oklahoma, presented safety data on the two trials at the
Chemotherapy Foundation Symposium XVII.
Edrecolomab was approved in Germany in 1994, but is investigational
in the United States. In early clinical trials, it was shown to
decrease overall mortality in resected colorectal cancer by 32% and
recurrence by 23%, compared with observation alone.
Dr. Keller said that edrecolomab is assumed to act as an
antibody-dependent cytotoxin and a complement-mediated cytolytic.
Because it is a murine antibody, human antimouse antibody (HAMA)
formation after the first treatment may inactivate the drug, Dr.
Keller said. It may, however, also enhance the effect of the drug by
generating an anti-idiotype network.
The first trial, being conducted in North and South America, compared
the safety and efficacy of the standard Mayo Clinic adjuvant regimen
(5-FU/leucovorin) with the standard regimen plus edrecolomab in 1,800
patients. The second trial, with 2,700 patients, added a third
armedrecolomab as a single agent.
The two studies are fully enrolled, and patients are currently being
followed for recurrence and survival. Interim efficacy analysis
should be available in the spring of 2000, Dr. Keller said.
He reported a tolerable safety profile for the agent based on the two
studies. The most common adverse events are those associated with
5-FU: diarrhea, nausea, abdominal pain, mucositis, and vomiting. The
incidence of these events was similar to that observed in the absence
of edrecolomab, with the exception of abdominal pain, which occurs
twice as frequently when edrecolomab is added to the standard
regimen. Neutropenia and leukopenia were reported in similar numbers
in the 5-FU/leucovorin and 5-FU/leucovorin/edrecolomab arms.
Dr. Keller concluded that edrecolomab is well tolerated as a single
agent and in combination with 5-FU/leucovorin. Its tolerability
and safety profile, combined with positive phase III efficacy
results, should lead to its acceptance as a standard of care with
5-FU, he said, and it may be readily combined with newer
agents coming into use.