Induction of remission in hepatocellular carcinoma with a new thymidylate synthase inhibitor, CB3717. A phase II study.
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.
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000188:drug therapy*; D004341:Drug Evaluation; D005260:Female; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000627:therapeutic use*; D012074:Remission Induction; D000509:alpha-Fetoproteins / Q000032:analysis
D011799:Quinazolines; D000509:alpha-Fetoproteins; C031662:CB 3717; D005492:Folic Acid