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.
- 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.