A Phase II trial of nolatrexed dihydrochloride in patients with advanced hepatocellular carcinoma.

Abstract

BACKGROUND:

Inoperable hepatocellular carcinoma is an incurable malignancy with no accepted standard therapy. Chemotherapy has demonstrated occasional responses and the need is great for a new and effective agent. Therefore the authors conducted this Phase II trial of a novel thymidylate synthase inhibitor, nolatrexed dihydrochloride (designed using structure-based computer modeling), in patients with advanced hepatocellular carcinoma.

METHODS:

Forty-one patients with unresectable or metastatic hepatocellular carcinoma were treated with nolatrexed, which was administered as a 24-hour outpatient intravenous infusion for 5 days at a dose of 795 mg/m2/day as free base (1000 mg/m2/day as salt) during each 21-day cycle. Prophylactic treatment was given for emesis and rash.

RESULTS:

Twenty-eight patients received at least 2 courses of treatment and 26 patients were evaluable. Two patients (8%) achieved a partial response and 2 additional patients achieved a minor response that was significant enough to allow surgical resection with curative intent. Fourteen patients (54%) achieved stable disease. The overall median survival was 7 months (10 months among patients who completed 2 cycles) and 1 patient remained free of disease at last follow-up, 37 months after surgery. Toxicity was modest and generally was comprised of stomatitis, nausea, malaise, and rash.

CONCLUSIONS:

Nolatrexed appears to have modest biologic activity in hepatocellular carcinoma. Due to the lack of alternative treatments, further study of this drug or an oral equivalent may be warranted.

• Authors: K Stuart, J Tessitore, J Rudy, N Clendennin, A Johnston
• Journal: Cancer (Cancer) Vol. 86 Issue 3 Pg. 410-4 (Aug 01 1999) ISSN: 0008-543X [Print] United States
• PMID: 10430248 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Quinazolines
• Thymidylate Synthase
• nolatrexed

Topics

• Adult
• Aged
• Antimetabolites, Antineoplastic (adverse effects, therapeutic use)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Female
• Humans
• Liver Neoplasms (drug therapy, pathology)
• Male
• Middle Aged
• Neoplasm Staging
• Quinazolines (adverse effects, therapeutic use)
• Survival Analysis
• Thymidylate Synthase (antagonists & inhibitors)