Phase II trial of cisplatin plus temozolomide, in recurrent and progressive malignant glioma patients

J Neurooncol. 2004 Jan;66(1-2):203-8. doi: 10.1023/b:neon.0000013479.64348.69.


We report a phase II trial of cisplatinum and temozolomide (TMZ) combination in recurrent malignant glioma patients. The DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGAT) is important in glioblastoma resistance to alkylating antitumor agents. In vitro, cisplatin (CDDP) decreases MGMT activity in a time- and dose-dependent manner. Thirty-three recurrent malignant glioma patients (20 GBM-13 AA) were treated at recurrence or progression with a CDDP and TMZ association. On days 1 and 2, iv CDDP (40 mg/sqm) was administered. TMZ (at the dose of 200 mg/sqm) was administered as a single oral daily-dose on days 2-6 (starting 24 h after the first CDDP dose), the cycle was repeated every 4 weeks. All patients had been previously treated with surgery followed by radiotherapy and CDDP + BCNU chemotherapy. The primary endpoint of the study was progression free survival at 6 months (PFS-6). Secondary endpoints included radiological response and toxicities. Thirty-three patients received a total of 113 courses (median 3 range 1-11). Complete responses were not observed, partial responses were 18.8% with an additional 39.9% of stable disease. For the whole group of patients the PFS at 6 and 12 months was 52% and 15% with a median TTP of 33 weeks. PFS-6 for GBM and Anaplastic astrocytoma (AA) were 35% and 69%, respectively. PFS-12 for GBM and AA were 13.8% and 17.3%, respectively. Median TTP was 21.3 and 39.5 weeks, respectively. The principal toxic effects of the regimen were: neutropenia (5 WHO grade IV), thrombocytopenia (4 WHO grade IV), nausea and vomiting.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Blood / drug effects
  • Brain Neoplasms / drug therapy*
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Dacarbazine / administration & dosage
  • Dacarbazine / adverse effects
  • Dacarbazine / analogs & derivatives*
  • Disease Progression
  • Drug Administration Schedule
  • Female
  • Glioma / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Survival Analysis
  • Temozolomide


  • Antineoplastic Agents
  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • Cisplatin
  • Temozolomide