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In a Phase II clinical trial, 14 consecutive, unselected patients with primary hepatocellular carcinoma were treated with a new inhibitor of thymidylate synthase, CB3717. On the basis of previously reported criteria, 6 patients were considered to have a good prognosis (Grade A) and 8 a poor prognosis (Grade B). Three Grade B patients died after only one treatment. Six patients responded (4 Grade A and 2 Grade B) with a decrease in tumour size and greater than 50% fall in serum alphafetoprotein levels; 3 of these had a greater than 1 log fall in alphafetoprotein. A further patient (Grade B) showed static disease during treatment. Thus, of 11 patients receiving two or more treatments 7 showed clinical benefit, with a median survival from start of CB3717 therapy of 46 weeks (2 still alive at 33 and 67 weeks). Our results suggest that CB3717 will be a useful new therapeutic agent in hepatocellular carcinoma. Further controlled trials are indicated to confirm these preliminary findings, using the drug both as a single agent and in combination with inhibitors of thymidine uptake by cells, which may further increase efficacy.


Journal article


J Hepatol

Publication Date





349 - 356


Adult, Aged, Carcinoma, Hepatocellular, Drug Evaluation, Female, Folic Acid, Follow-Up Studies, Humans, Liver Neoplasms, Male, Middle Aged, Quinazolines, Remission Induction, alpha-Fetoproteins