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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.

The change of lactic acid concentration in the tumour after intraperitoneal administration of 5 g/kg glucose, and the effect of the lactic acid concentration on antitumour activity of hyperthermia were studied in an experimental murine tumour. The lactic acid concentration in SCC VII tumours transplanted into the legs of C3H/HeJ male mice was measured by gas chromatography. Local hyperthermic treatment to the tumour was performed with a water bath at 43 degrees C for 40 min. Antitumour effects were evaluated by measuring tumour volume doubling time (DT) as an index. The mean concentration of lactic acid in the tumour was 10.4 mumol/g in the no-treatment group. The lactic acid concentration gradually increased after glucose administration, reaching a significantly high concentration of 20.0 mumol/g at 90 min later. The DTs in the no-treatment group and hyperthermia alone group were 2.4 and 3.7 days respectively. The DTs in the glucose administration groups shortly before, 30 and 60 min before the hyperthermia were 3.6, 3.6 and 5.6 days respectively. The DT in the 60 min group was significantly extended (p0.0001). Hyperthermia during the period of increased lactic acid concentration significantly prolonged the DT of the tumour. These results clearly showed that an increase of lactic acid concentration in the tumour improved the effect of local hyperthermia.

1. 1. The water content of rabbit erythrocytes was measured by gas-liquid chromatography to observe the effects of thermal stress on water content. 2. 2. The water content of erythrocytes was decreased immediately after 45-min whole-body heating at 42°C compared to heating at 37°C. 3. 3. The water content of erythrocytes was increased after heating in vitro at 42°C for 1 h compared with the values after treating at 37°C and the control value.