A PHASE-II STUDY OF ORAL PIRITREXIM IN RECURRENT HIGH-GRADE (III, IV)GLIOMA

Piritrexim is a lipid-soluble drug which is as effective an inhibitor of dihydrofolate reductase as methotrexate. Phase I and II studies hav e indicated activity in some tumour types. Because of its lipophilicit y we have conducted a phase II study in recurrent high-grade malignant glioma (grades LII and IV). Twenty-seven patients were treated with 2 5 mg p.o. three times daily for five consecutive days, repeated weekly , with provision for dose escalation or reduction according to toxicit y. Five patients received less than 4 weeks' treatment because of dise ase progression or death. Twenty-two patients were evaluable for respo nse. One complete and one partial response was seen (duration 262+ and 241+ weeks) and 13 patients had static disease for a median duration of 13 weeks (range 7-35). The major toxicity was myelosuppression. Thi s response rate of 9% of evaluable patients is much lower than that se en for some conventionally used drugs and we conclude that piritrexim is unlikely to be of value in the management of high-grade gliomas.