NEW YORK—A monoclonal antibody (MoAb) is being studied as monotherapy and in combination with standard fluorouracil(Drug information on 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 arm—edrecolomab 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.”
