Centocor Inc.'s monoclonal antibody Panorex reduced the overall death rate of patients with stage C colorectal cancer by 30 percent after a median five-year follow-up, according to results of a Phase III study.

The prospective randomized trial, conducted in Germany, involved 189 patients who had undergone curative surgery. Investigator Gert Riethmller of the Institut fur Immunologie der Universitat presented the findings on Tuesday at the annual meeting of the German and Austrian Society for Hematology and Oncology in Essen.

"Numerous failed clinical trials with monoclonal antibody have led to a general demise of passive antibody therapy for solid tumors," according to an abstract of the study. One possible explanation "has been insufficient accessibility and heterogenicity of tumor cells in advanced solid metastases." Therefore, the clinical trial focused on "minimal residual disease in colorectal cancer Dukes C after curative surgery, targeting 17-1A, a murine IgG2A antibody to dispersed epithelial tumor cells."

After surgery, patients were randomized to receive 17-1A antibody (Panorex) treatment or no therapy. In addition to decreasing the mortality rate by 30 percent (log rank: p=0.05, cox proportional hazard: p=0.04), Panorex also decreased the rate of cancer recurrence by 27 percent.

Investigators found only minor and infrequent side effects with the antibody treatment -- mainly mild general and gastrointestinal symptoms. Immunogenicity of the antibody was low and antibody titers were induced in all treated patients.

According to the study, four anaphylactic reactions were observed out of 371 infusions; none required hospitalization.

Panorex is directed against an antigen found on the surface of colorectal cancer cells as well as other types of cancer cells, including breast and lung cancer.

Chaunce Bogard, Centocor's vice president of project management, told BioWorld that Panorex has three possible mechanisms of action. When the antibody binds to the antigen, it can either evoke antibody-dependent cell cytotoxicity -- turning on cytotoxic cells that kill the cancer cells -- or trigger the complement system, which results in putting a hole in the targeted cell, thereby destroying the cell's osmotic balance and causing it to burst. Bogard said there is in vitro evidence that the antibody can do both, but it is not known which mechanism leads to activity in patients.

A third potential mechanism of action relates to the antibody itself. Bogard said Panorex is a mouse antibody that may be recognized by the body as foreign and evoke an immune response.

Centocor (NASDAQ:CNTO) of Malvern, Pa., plans to file an application for marketing approval in Germany early next year. The company also will conduct Phase III clinicals in the U.S. and Europe next year to confirm the German trial.

David Holveck, Centocor's president and chief executive officer, noted that a future trial will probably involve a comparison with 5-FU/levamisole, which is the standard treatment for colorectal cancer in the U.S. and some European countries.

Future regulatory filings and clinical trials will be done in conjunction with Wellcome plc. Centocor formed a partnership with the British pharmaceutical company last month to develop and bring to market Centocor's oncology products, primarily Panorex.

Centocor's stock gained $3 a share on Tuesday, closing at $14.25.

-- Brenda Sandburg News Editor

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