Centocor Inc.'s monoclonal antibody Panorex reduced theoverall death rate of patients with stage C colorectal cancer by30 percent after a median five-year follow-up, according toresults 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 Immunologieder Universitat presented the findings on Tuesday at theannual meeting of the German and Austrian Society forHematology and Oncology in Essen.
"Numerous failed clinical trials with monoclonal antibody haveled to a general demise of passive antibody therapy for solidtumors," according to an abstract of the study. One possibleexplanation "has been insufficient accessibility andheterogenicity of tumor cells in advanced solid metastases."Therefore, the clinical trial focused on "minimal residualdisease in colorectal cancer Dukes C after curative surgery,targeting 17-1A, a murine IgG2A antibody to dispersedepithelial tumor cells."
After surgery, patients were randomized to receive 17-1Aantibody (Panorex) treatment or no therapy. In addition todecreasing the mortality rate by 30 percent (log rank: p=0.05,cox proportional hazard: p=0.04), Panorex also decreased therate of cancer recurrence by 27 percent.
Investigators found only minor and infrequent side effectswith the antibody treatment -- mainly mild general andgastrointestinal symptoms. Immunogenicity of the antibodywas low and antibody titers were induced in all treatedpatients.
According to the study, four anaphylactic reactions wereobserved out of 371 infusions; none required hospitalization.
Panorex is directed against an antigen found on the surface ofcolorectal cancer cells as well as other types of cancer cells,including breast and lung cancer.
Chaunce Bogard, Centocor's vice president of projectmanagement, told BioWorld that Panorex has three possiblemechanisms 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 triggerthe complement system, which results in putting a hole in thetargeted cell, thereby destroying the cell's osmotic balance andcausing it to burst. Bogard said there is in vitro evidence thatthe antibody can do both, but it is not known which mechanismleads to activity in patients.
A third potential mechanism of action relates to the antibodyitself. Bogard said Panorex is a mouse antibody that may berecognized by the body as foreign and evoke an immuneresponse.
Centocor (NASDAQ:CNTO) of Malvern, Pa., plans to file anapplication 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 comparisonwith 5-FU/levamisole, which is the standard treatment forcolorectal cancer in the U.S. and some European countries.
Future regulatory filings and clinical trials will be done inconjunction with Wellcome plc. Centocor formed a partnershipwith the British pharmaceutical company last month to developand bring to market Centocor's oncology products, primarilyPanorex.
Centocor's stock gained $3 a share on Tuesday, closing at$14.25.
-- Brenda Sandburg News Editor
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