Eflornithine (DFMO), an irreversible inhibitor of
ornithine decarboxylase, and
mitoguazone (
MGBG), a competitive inhibitor of
S-adenosylmethionine decarboxylase, were evaluated in a phase I-II study for patients with primary recurrent malignant
brain tumors. All patients had failed prior
radiation therapy and most had also failed prior
chemotherapy. Two dose schedules were used, with the second schedule (Group II) a modification of the first schedule (Group I). The Group II schedule, with different dose levels, was better tolerated than the Group I schedule. Gastrointestinal and myelotoxicity were dose-limiting in most patients, and
tinnitus was dose-limiting in two patients. Nineteen of 33 evaluable patients had anaplastic
gliomas, in whom response was observed in 21%, stable disease in 53%, and immediate progression after one course of
therapy in 26%. Of six patients with
glioblastoma multiforme, two had brief stabilization of disease. An additional patient with brainstem
glioma and
ependymoma also had disease stabilization. Four patients with
medulloblastoma, a spinal cord
mixed glioma, and one with
oligodendroglioma failed DFMO-
MGBG. Based on this study, we believe that a combination of DFMO and
MGBG is well-tolerated and deserves further evaluation for patients with anaplastic
gliomas, particularly those that appear to be biologically slow growing.