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A phase II one-arm study was performed to evaluate the efficacy and safety of concurrent chemoradiotherapy with the use of uneven fractionation in glioblastoma patients. A total of 19 glioblastoma patients underwent concurrent chemoradiotherapy with the use of uneven fractionation. Vincristine (VCR) and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU) were administered on day 1 and day 2, respectively. Irradiation at a dose of 3 Gy was administered on days 3 and 4, and at a dose of 1.5 Gy from day 5 on. The treatment was repeated at 10 day intervals. The total radiation dose was 57 Gy. All 19 patients received full dose irradiation. However, 8 patients required treatment interruption, and 2 patients required decreases in drug dosages due to the effects of acute toxicity such as, myelosuppression, liver function disorder and skin toxicity. The treatment responses were recorded as CR in 5, PR in 1, and NC in 10 patients. The remaining three patients received total removal of the enhancing area on CT or MRI. The 1 year and 2 year survival rates were 73% and 23%, respectively. The median survival times of this study and the historical controls were 16 months and 15 months, respectively. The concurrent chemoradiotherapy failed to prolong the survival of glioblastoma patients.