Induction of remission in hepatocellular carcinoma with a new thymidylate synthase inhibitor, CB3717. A phase II study.

Abstract

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.

• Authors: M F Bassendine, N J Curtin, H Loose, A L Harris, O F James
• Journal: Journal of hepatology (J Hepatol) Vol. 4 Issue 3 Pg. 349-56 (Jun 1987) ISSN: 0168-8278 [Print] Netherlands
• PMID: 2439582 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Quinazolines
• alpha-Fetoproteins
• CB 3717
• Folic Acid

Topics

• Adult
• Aged
• Carcinoma, Hepatocellular (diagnosis, drug therapy)
• Drug Evaluation
• Female
• Folic Acid (analogs & derivatives, therapeutic use)
• Follow-Up Studies
• Humans
• Liver Neoplasms (diagnosis, drug therapy)
• Male
• Middle Aged
• Quinazolines (therapeutic use)
• Remission Induction
• alpha-Fetoproteins (analysis)