Trimetrexate in malignant mesothelioma: A Cancer and Leukemia Group B Phase II study.
OBJECTIVE
Folic acid antagonists are reported to have activity against mesothelioma. The Cancer and Leukemia Group B (CALGB) undertook this phase II study of the new antifolate, trimetrexate (TMTX), to evaluate its response rate and toxicity in chemotherapy-naive patients with malignant mesothelioma.


METHODS
Fifty-two patients were accrued to this protocol. Because of concerns about TMTX toxicity in patients with malignant effusions and/or hypoalbuminemia, the first 17 patients were treated at a dose of 6 mg/m2 daily for 5 days every 21 days. Because minimal toxicity was observed, the subsequent 35 patients were treated at a dose of 10 mg/m2.


RESULTS
Two of 17 patients (12%) in the 6-mg/m2 treatment group had a partial response (PR) and four of 34 eligible patients (12%) in the 10-mg/m2 treatment group had a PR or regression (R) of assessable disease. No patient achieved a complete response (CR). Median survival durations were 5.0 and 8.9 months in the 6- and 10-mg/m2 treatment groups, respectively, while the 2-year survival rates were identical at 18%. At the 10-mg/m2 dose, toxicity was tolerable, with one toxic death from sepsis and a 12% rate of grade 4 thrombocytopenia and granulocytopenia.


CONCLUSIONS
In this large trial, TMTX showed minor activity in the treatment of malignant mesothelioma. Myelosuppression was mild and dose-related. Future studies of higher doses of TMTX should be considered.
Department of Medicine, University of Chicago, IL 60637-1470.
N J
NJ
Vogelzang
L B
LB
Weissman
J E
JE
Herndon
K H
KH
Antman
M R
MR
Cooper
J M
JM
Corson
M R
MR
Green
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy*; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome; D016597:Trimetrexate / Q000009:adverse effects / Q000627:therapeutic use*
D016597:Trimetrexate