NOA-05 phase II trial of procarbazine and CCNU therapy in gliomatosis cerebri

Annals of Neurology , 05/13/2011

Glas M et al. – Procarbazine and CCNU(PC) chemotherapy is effective in gliomatosis cerebri(GC). With the NOA–05 trial being the first prospective multicenter trial in GC, PC chemotherapy can be regarded as a promising option for the primary therapy of these tumors.

Methods

  • 35 patients with previously untreated GC were treated with up to six 56–day courses of 110 mg/m2 CCNU on day 1 and 60 mg/m2 procarbazine on days 8 to 21.
  • Primary endpoint was the rate of patients without therapy failure (defined as progressive disease, death from any cause or termination of PC therapy before the end of course 4) at 8 months after the beginning of PC chemotherapy.

Results

  • Failure–free survival rate at 8 months was 50.3%.
  • Median progression–free survival was 14 months.
  • At progression, 12 patients received salvage radiotherapy.
  • Median overall survival was 30 months. Multivariate analysis revealed isocitrate dehydrogenase 1 (IDH1) gene mutation (hazard ratio (HR) 0.11, 95%CI 0.02–0.58) and initial presentation without a bilateral symmetrical infiltration pattern on MRI (HR 0.07, 95%CI 0.01–0.54) as independent prognostic factors associated with prolonged survival.
  • DH1 mutation was significantly associated with MGMT promoter methylation and an oligodendroglial tumor component.

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