Investigational New Drug Program, NCIC Clinical Trials Group, Kingston, Biochem Pharma, Laval, Canada. BCH-4556 is a stereochemically non natural cytidine analogue. The compound inhibits DNA polymerases, is a chain terminator, but is not a substrate for cytidine deaminase. Preclinical cytotoxic activity has been demonstrated in a variety of human xenograft models including renal, prostate, colon, lung and leukemia.
Activity is dose and schedule dependent.
Preclinical toxicology revealed marked interspecies differences. The starting dose was 0.025 mg m2. Thirty-six patients have been registered to date. Thirty-six patients are currently evaluable for toxicity. Myelosuppression has become more common with increasing dose levels, but remains generally mild and without significant clinical impact.