PHASE-II TRIAL OF EDATREXATE IN PATIENTS WITH ADVANCED HEPATOCELLULAR-CARCINOMA

Background: The methotrexate analogue edatrexate (10-ethyl-10-deaza-aminopterin, or 10-EDAM) has demonstrated greater activity than methotrexate has against murine tumors and human tumor xenografts. Phase II trials of edatrexate have already demonstrated its activity against breast, lung, and head and neck carcinomas. A phase II trial of edatrexate was conducted in patients with advanced hepatocellular carcinoma. Patients and methods: Seventeen patients with previously untreated unresectable hepatocellular carcinoma were enrolled on the study. Edatrexate, 80 mg/m2 weekly for 5 weeks, was administered intravenously. The treatment course was repeated every 6 weeks. Tumor response was evaluated by computerized tomographic scan after 2 courses. Results: No complete or partial responses were observed in this trial. Two minor responses, each lasting less than 12 weeks, were observed. Twelve patients had elevated serum alpha-fetoprotein (AFP) levels at entry into the study; 4 of the 12 patients experienced a greater-than-or-equal-to 25% decrease in the level of this tumor marker; 3 of the 4 had a >50% reduction in AFP level. Grade 3 and 4 toxic effects were granulocytopenia, thrombocytopenia, anemia, oral mucositis, skin reactions, fatigue, anorexia, and diarrhea. Conclusions: Edatrexate administered at this dose and schedule appears to have little therapeutic efficacy against advanced hepatocellular carcinoma.