title: Phase II study on cisplatin and ifosfamide in recurrent high grade gliomas.
abstract: 27 patients with recurrent high grade glioma following surgery and radiation therapy were treated with 100 mg/m2 cisplatin and 6 g/m2 ifosfamide per cycle, administered on days 1-3 in 4 week cycles, for a maximum of six cycles. Toxicity was assessed after every cycle. Response was assessed following every second cycle, and a 50% decrease of the largest cross-sectional tumour area on contrast enhanced magnetic resonance imaging or computed tomography scan was considered a partial response (PR). A total of 95 cycles was administered; 26 patients were evaluable for response. In 5 patients (19%), a PR was obtained (median time to progression (TTP): 34 weeks). Stable disease was observed in 6 patients (23%, median TTP: 22 weeks). The most frequent toxicity was haematological: 37% of cycles were complicated by a grade 3 or 4 leucopenia. 1 patients died, probably as a consequence of increased cerebral oedema induced by the cisplatin hydration schedule. Determination of the cisplatin concentration in this patient showed a 10-fold increase in the tumour concentration as compared with that in normal brain tissue, demonstrating the absence of a blood-brain barrier in the tumour. In conclusion, generally this schedule was well tolerated, but it is of moderate activity for recurrent glioma.
authors.affiliation: Department of Neuro-Oncology, Rotterdam Cancer Institute, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: van den Bent
authors.forename: J H
authors.initials: JH
authors.lastname: Schellens
authors.forename: C J
authors.initials: CJ
authors.lastname: Vecht
authors.forename: P A
authors.initials: PA
authors.lastname: Sillevis Smit
authors.forename: O J
authors.initials: OJ
authors.lastname: Loosveld
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.forename: C C
authors.initials: CC
authors.lastname: Tijssen
authors.forename: R L
authors.initials: RL
authors.lastname: Jansen
authors.forename: J M
authors.initials: JM
authors.lastname: Kros
authors.forename: J
authors.initials: J
authors.lastname: Verweij
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016896:Treatment Outcome
chemical_list: D002945:Cisplatin; D007069:Ifosfamide