COMBINED MODALITY TREATMENT USING RADIATION AND OR CHEMOTHERAPY IN AN ATHYMIC NUDE MOUSE-HUMAN MEDULLOBLASTOMA AND GLIOBLASTOMA XENOGRAFT MODEL

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (3) , 812-816
Abstract
A human medulloblastoma (BN-2) and a glioblastoma (BN-3) previously established in nude mice were used to determine the effect of combined modality therapy with .gamma.-radiation and 3 chemotherapeutic agents, procarbazine, 1,4-cyclohexadiene-1,4-dicarbamic acid, 2,5-bis(1-aziridinyl)-3,6-dioxodiethylester (AZQ), and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The tumor cells were grown in tissue culture and implanted intracranially in the right cerebral hemisphere of NIH Swiss nude mice to a depth of 3 mm. The mice were randomized and treatment was started 3 days after tumor implantation. Procarbazine and AZQ were injected i.p. every 5 days for 3 treatments. BCNU was injected 1 time for a single treatment. Radiation was localized to the head. A 60Co unit was used for irradiation at the rate of 125 rad/min 3 days after tumor implantation. Ten experiments were performed using 6-9 mice/group and different drug-radiation dose combinations. The drug dose ranged from 400-500 mg/kg per injection for procarbazine, 7.5 mg/kg per injection for AZQ, and 10-20 mg/kg per injection for BCNU. The radiation dose ranged from 320-1050 rad/mouse (whole head). The day of death was recorded for each animal, and the mean of each treatment group was used to calculate the percentage increase in life span (ILS) compared to the untreated control group. Chemotherapy alone produced a minimal effect, while radiation alone produced minimal effects at 320-640 rad with progressively positive effects at 800 and 1050 rad. When the combination treatment of the human medulloblastoma xenograft with procarbazine was used, the ILS was significantly increased in all 4 experiments, ranging from 25-41%, and was superior to single-modality treatment in all but the 1050 rad treatment, where it showed an equal effect. The combination treatment using AZQ and BCNU showed no ILS for the medulloblastoma tumor. Combination treatment of the human glioblastoma xenograft using BCNU produced significant ILS of 105 and 119% and was superior to single-modality treatment with a drug dose of 10 mg/kg and radiation doses of 540 and 800 rad, respectively. The nude mouse-human tumor xenograft model was useful for combined modality studies and should give valuable information for the experimental design of pilot Phase III clinical [human] studies against a variety of brain tumors.