title: First-line chemotherapy with cisplatin plus fractionated temozolomide in recurrent glioblastoma multiforme: a phase II study of the Gruppo Italiano Cooperativo di Neuro-Oncologia.
abstract: OBJECTIVE
  Cisplatin and temozolomide (TMZ) are active in glioblastoma multiforme (GBM), with different profiles of toxicity. A bid regimen of TMZ achieves a strong inhibition of O(6)-alkylguanine DNA-alkyl transferase (AGAT), and cisplatin reduces AGAT activity in vitro, suggesting a possible synergic interaction. The primary end point of the present multicenter phase II study was progression-free survival (PFS) at 6 months (PFS-6); secondary end points included response, toxicity, and overall survival.
  
  
  METHODS
  Chemotherapy-naive patients with GBM who experienced disease recurrence or progression after surgery and standard radiotherapy were eligible. Chemotherapy cycles consisted of cisplatin 75 mg/m(2) on day 1, TMZ 130 mg/m(2) bolus followed by nine doses of 70 mg/m(2) every 12 hours (total of 5 days) from day 2 every 4 weeks. In the absence of hematologic toxicity, TMZ was escalated to 1,000 mg/m(2) in 5 days.
  
  
  RESULTS
  A total of 50 patients (median age, 53.4 years; range, 27 to 70 years; median Karnofsky performance status, 80; range, 60 to 100) were accrued in the study. PFS-6 was 34% (95% CI, 23% to 50%), and PFS-12 was 4% (95% CI, 0.3% to 16%). Median PFS was 18.4 weeks (95% CI, 13 to 25.9 weeks). Among 49 assessable patients, one complete response and nine partial responses were obtained, with an overall response rate of 20.4% (95% CI, 7.7% to 33%). Among 203 treatment cycles delivered, the most common grade 3 or grade 4 events included granulocytopenia in 7.9% of cycles, thrombocytopenia in 4%, and neurologic toxicity in three patients (6%).
  
  
  CONCLUSIONS
  The new cisplatin plus bid TMZ regimen appears active in chemotherapy-naive patients with recurrent GBM and incurs an acceptable toxicity.
authors.affiliation: Department of Medical Oncology-Direzione, Azienda Ospedale-Università Ospedale Busonera, Via Gattamelata 64, 35100 Padua, Italy. aabrandes@unipd.it
authors.forename: Alba A
authors.initials: AA
authors.lastname: Brandes
authors.forename: Umberto
authors.initials: U
authors.lastname: Basso
authors.forename: Michele
authors.initials: M
authors.lastname: Reni
authors.forename: Francesca
authors.initials: F
authors.lastname: Vastola
authors.forename: Alicia
authors.initials: A
authors.lastname: Tosoni
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cavallo
authors.forename: Luciano
authors.initials: L
authors.lastname: Scopece
authors.forename: Andres J
authors.initials: AJ
authors.lastname: Ferreri
authors.forename: Maria G
authors.initials: MG
authors.lastname: Panucci
authors.forename: Silvio
authors.initials: S
authors.lastname: Monfardini
authors.forename: Mario
authors.initials: M
authors.lastname: Ermani
mesh_terms: D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D000077204:Temozolomide; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D003606:Dacarbazine; D002945:Cisplatin; D000077204:Temozolomide