Abstract
In order to establish the standard therapy for malignant gliomas, the JCOG-Brain Tumor Study Group was organized in 2002 and started a phase II/III study. It is investigating the efficacy of procarbazine+ACNU+radiation compared to ACNU+radiation which is considered to be the standard therapy for malignant gliomas. Patients with astrocytoma grade 3 or 4 are randomized into two groups postoperatively. Patients in Arm A receive intravenous injection of ACNU on day 1 and day 36 of radiotherapy. Those in Arm B receive oral procarbazine for 10 days before injection of ACNU. Procarbazine is reported to reduce O^6-methylguanine-DNA methyltransferase(MGMT) activity and enhance the anti-cancer effect of nitrosoureas. Recently many studies have been started to overcome chemo-resistance. A trial of the individualization of the treatment, the so-called taylor-made therapy, is one of the challenges for treatment. Loss of chromosome 1p and 19q is considered to be closely related to chemo-sensitivity in anaplastic oligodendrogliomas. Procarbazine+CCNU+vincristine (PCV) therapy is very effective in tumors with 1p and 19q losses compared to those without these losses. This is one of the epoch making findings in the field of chemotherapy for malignant brain tumors. MGMT is a DNA repair enzyme which reduces the anti-cancer effect of nitrosourea. In order to overcome this chemo-resistance nitrosourea or drugs which reduce the MGMT activity such as procarbazine or O^6-benzylguanine are used for those tumors expressing MGMT. However, even in Taylor-made therapy prospective randomized studies under good quality control and quality assurance are essential to establish an evidence-based treatment.
