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Clinical Trials |
Ottawa Regional Cancer Centre, Ottawa, Ontario, K1H 8L6 Canada [M. C. C.]; Hamilton Regional Cancer Centre, Hamilton, Ontario, Canada [A. L. F.]; Princess Margaret Hospital, Toronto, Ontario, Canada [A. M. O.]; London Regional Cancer Centre, London, Ontario Canada [M. J. T.]; Cross Cancer Institute, Edmonton, Alberta, Canada [A T. F.]; Isis Pharmaceuticals, Carlsbad, California [J. T. H., R. S. G.]; and National Cancer Institute of Canada, Clinical Trials Group, Kingston, Ontario, K7L 3N6 Canada [L. W. M., E. A. E.]
Background: Because treatment of metastatic colon cancer is noncurative, new treatments are needed. This trial evaluated the antitumor effects of two targeted anticancer agents: (a) ISIS 3521, an antisense inhibitor of the protein kinase C 
; and (b) ISIS 5132, an antisense inhibitor of c-raf kinase in patients untreated previously with recurrent or metastatic colorectal carcinoma.
Patients and Methods: All patients had colorectal adenocarcinoma with measurable disease and no prior chemotherapy for metastatic disease. Patients were randomized to receive either ISIS 3521 or ISIS 5132 at a dose of 2 mg/kg/day as a continuous i.v. infusion 21 of 28 days. Cycles were repeated as long as progression was not seen, and doses of both agents were modified according to toxic effects. A two-arm study design was used with each study arm considered independently. Steady-state blood levels of both antisense molecules were measured on days 8, 15, and 22 of the first cycle of therapy.
Results: Thirty-seven eligible patients were enrolled, and 32 were evaluable for response (17 receiving ISIS 3521 and 15 receiving ISIS 5132). No responses were noted. Four of the patients receiving ISIS 3521 had stable disease, and 5 patients receiving ISIS 5132 were stable.
Conclusion: Neither ISIS 5132 nor ISIS 3521given in the dose and schedule studied induced objective responses in untreated colorectal cancer patients.
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