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.


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 > or = 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.
Pazdur
R
R
Division of Medicine, University of Texas M.D. Anderson Cancer Center, Houston.
Moore
D F
DF
Bready
B
B
Giannone
L
L
Maldonado
A
A
Lin
Y G
YG
Fueger
R H
RH
Winn
R J
RJ
Levin
B
B
D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced; D000630:Aminopterin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005493:Folic Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D013921:Thrombocytopenia / Q000139:chemically induced; D000509:alpha-Fetoproteins / Q000378:metabolism
D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D000509:alpha-Fetoproteins; C040210:edatrexate; D000630:Aminopterin