Agouron Begins Phase II Testing of AG 337

Clinical progress reported in a Phase I trial of Agouron Pharmaceuticals' anticancer drug AG 337 has stimulated the company to enter the compound into Phase II testing in the USA.

AG 337 is a non-classical antifolate inhibitor of thymidylate synthase, the terminal enzyme involved in the de novo synthesis of thymidylate in the body, which is important for DNA synthesis. The results of a Phase I study of AG 337, which involved a five-day continuous infusion of the drug given every three weeks to 19 patients with advanced-stage solid tumors, were presented at the American Association for Cancer Research meeting last month.

The starting dose in this Phase I trial was 120mg/m2/day, while the maximum tolerated dose was 1,130mg/m2/day. There was one partial response among the 19 patients, in a colorectal cancer patient who had received prior treatment with 5-fluorouracil. Hematological and gastrointestinal toxicities were most significant, although mucositis was also a problem. Nausea and vomiting was moderate during the infusion period.