title: A phase II study of oral piritrexim in recurrent high-grade (III, IV) glioma.
abstract: Piritrexim is a lipid-soluble drug which is as effective an inhibitor of dihydrofolate reductase as methotrexate. Phase I and II studies have indicated activity in some tumour types. Because of its lipophilicity we have conducted a phase II study in recurrent high-grade malignant glioma (grades III and IV). Twenty-seven patients were treated with 25 mg p.o. three times daily for five consecutive days, repeated weekly, with provision for dose escalation or reduction according to toxicity. Five patients received less than 4 weeks' treatment because of disease progression or death. Twenty-two patients were evaluable for response. 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. This response rate of 9% of evaluable patients is much lower than that seen for some conventionally used drugs and we conclude that piritrexim is unlikely to be of value in the management of high-grade gliomas.
authors.affiliation: University Department, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: N M
authors.initials: NM
authors.lastname: Bleehen
authors.forename: H V
authors.initials: HV
authors.lastname: Newman
authors.forename: R P
authors.initials: RP
authors.lastname: Rampling
authors.forename: J R
authors.initials: JR
authors.lastname: Ramsay
authors.forename: J T
authors.initials: JT
authors.lastname: Roberts
authors.forename: P
authors.initials: P
authors.lastname: Bedford
authors.forename: A B
authors.initials: AB
authors.lastname: Nethersell
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005493:Folic Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D011743:Pyrimidines; C024530:piritrexim