CoFactor (Biokeys Pharmaceuticals).

BioKeys is developing CoFactor (methylenetetrahydrofolate), a thymidylate synthase inhibitor and modulator of 5-fluorouracil (5-FU), for the potential enhancement of cancer treatments using 5-FU [357795]. By March 2000, phase I/II trials had been completed and phase III trials were in preparation for the US and Scandinavia [357806,357795]. In November 2000, the company initiated a pharmacogenomic study of CoFactor [389157]. The company believes that genomic screening will be very useful for determining the most likely candidates for successful 5-FU/CoFactor therapy, therefore, Biokeys is undertaking a study on tissue samples from 62 patients who were previously treated in phase I/II trials. Analyses will be based upon a RT-PCR from paraffin-embedded tissues. This improved technology, which permits retrospective analyses from paraffin-fixed tissues, will enable BioKeys' scientists to better understand previous responses by the patients treated in the phase I/II trials [389157]. In phase I/II trials, CoFactor was administered to 62 cancer patients receiving 5-FU therapy and resulted in partial responses of 21 to 55% in colorectal, pancreas, stomach, gallbladder and breast cancer patients. Toxicity was milder than expected for 5-FU or 5-FU/leucovorin [357806,357795]. CoFactor has been shown to be 100-fold stronger than leucovorin in the promotion of thymidylate synthase inhibition [357795].