SYST-10 CSNO2012001 STUDY: A PHASE III TRIAL ON ADJUVANT TEMOZOLOMIDE CHEMOTHERAPY WITH OR WITHOUT INTERFERON-ALPHA IN NEWLY DIAGNOSED HIGH-GRADE GLIOMAS

PURPOSE: The therapeutic efficacy and toxicity of the combination of temozolomide (TMZ) with interferon-alpha (IFN-α) and TMZ alone were compared in newly diagnosed high-grade glioma (HGG) patients. PATIENTS AND METHODS: Following surgery, patients with newly diagnosed HGG were eligible and randomized into two groups. All the patients received standard radiotherapy concurrent with TMZ. After a 4-week break, patients in group A received standard TMZ (200mg/m2 for 5 days) combined with interferon-α (3mIU, subcutaneous, d1, d3, and d5) every 28 days. Patients in group B received standard TMZ. RESULTS: A total of 199 HGG patients were enrolled, with a median follow-up time of 77.9 months. The median overall survival (OS) of patients in the TMZ+IFN group was significantly longer than that in the standard group (TMZ+IFN: 26.67 months, TMZ: 18.83 months, P=0.005), although the progression-free survival (PFS) of both groups was similar (TMZ+IFN:14.83 months, TMZ:12.90months, P=0.114). In grade 3 gliomas, the median OS was 39.57 months in the TMZ+IFN group versus 29.40 months in TMZ alone (P=0.043). The median PFS was also longer in the TMZ+IFN group (24.33 months) than that in the TMZ group (14.13 months) (P=0.046). In grade 4 gliomas, the difference in PFS survival between TMZ+IFN and TMZ group showed no significant difference (TMZ+IFN:12.00 months, TMZ:12.83 months, P=0.582). However, the TMZ+IFN group had a longer OS than that of the TMZ alone group (TMZ+IFN:20.53 months, TMZ:17.70 months, P=0.044). TMZ+IFN also significantly improved the OS in O6-methylguanine-DNA methyltransferase (MGMT) unmethylation patients. The incidence of toxic effects such as neutropenia, thrombocytopenia, anemia, increased transaminase, skin reactions, fatigue, nausea, or vomiting, and skin reactions were similar in both groups. CONCLUSIONS: Compared with the standard regimen, TMZ+IFN combination treatment could prolong the survival time of HGG patients, especially MGMT promoter unmethylated patients, and the toxicity remained tolerable.