The potential antitumor effect of MX2, a new lipophilic
morpholino anthracycline, was compared with those of
ACNU or
doxorubicin (DOX) using two different rodent
glioma models. A mouse subcutaneous
glioma model (203
glioma) was used to measure the effect of each
drug on reducing the
glioma size and a rat 9L intracerebral
glioma model (9L
glioma) was used to assess the antitumor effect on survival rate in a clinically similar fashion. Treatment with
ACNU inhibited
tumor growth by 94.6% (p < 0.0001) and complete regression of the
tumor was observed in 3 of 25 (12.0%) of the
ACNU-treated cases.
Tumor growth was inhibited by 32.4% with DOX despite a tendency (p < 0.16) and by 59.4% with
MX-2 (p < 0.001); neither of these drugs resulted in complete
tumor regression. In the intracerebral
glioma rats, only
ACNU tended to ameliorate survival rate, but there was no statistical significance. These results suggest that
ACNU has the most potent effect but MX2 can be an option for
chemotherapy of
malignant gliomas. Interestingly, all three drugs significantly elevated the brain water content on both the ipsilateral and contralateral sides of the
tumor, although they did not induce
brain edema in the normal rat brains. Careful management of
brain edema might be required regardless of the
drug used during
chemotherapy to maximize the prognosis of
glioma patients.