COMBINATION OF AZIRIDINYLBENZOQUINONE AND CISPLATINUM WITH RADIATION-THERAPY IN THE 9L RAT-BRAIN TUMOR-MODEL

Purpose: We evaluated the potentiating effects of aziridinylbenzoquino ne (AZQ) and cis-platinum on the prolongation of survival by radiation therapy in a rat brain tumor model. Methods and Materials: On day 10 following intracranial inoculation of the 9L gliosarcoma, Fischer 344 rats were treated with radiation therapy (Cesium-137 source irradiator ) and/or chemotherapy delivered either systemically (intraperitoneal o r intravenous), or intracranially directly into the tumor in a volume of 5 mul. Increased life spans were calculated relative to the median survival time for the control (ILS-C) or to the median survival time f or radiation therapy only (ILS-RT) group. Results: Median survival tim e for untreated rats was 22 +/- 3 days for seven experiments. Radiatio n therapy (16 Gy) produced a significant (p < 0.002) improvement in su rvival, with an average ILS-C of 75 +/- 19%. Systemic AZQ (1 or 5 intr avenous injections of 0.5 mg/kg) produced ILS's of 0 and 23%, the latt er being significant (p = 0.002). When added to radiation therapy, the re were further improvements (ILS-RT's of 47 and 72%), but these were not significant. Intratumor AZQ (40 or 50 mug intracranially) produced significant ILS-C's of 30 and 33% (p = 0.01 and 0.0002, respectively) . Added to radiation therapy, intracranial AZQ produced improvements ( ILS-RT's of 5 and 102%), with only the latter being significantly impr oved (p = 0.009). Cis-platinum (3 mug intracranially) produced ILS-C's of 13 and 6%, neither significantly different from controls. Added to radiation therapy, cis-platinum caused improvements (ILS-RT's of 18 a nd 64%), with only the latter significant (p = 0.049). Conclusion: The se results demonstrate that AZQ delivered systemically, and AZQ and ci s-platinum delivered intracranially, can produce statistically signifi cant improvements in the survival of rats burdened with the 9L brain t umor. The agents delivered intracranially significantly potentiated th e prolongation of survival obtained by radiation therapy. This preclin ical evidence suggests that combining radiation therapy with these cyt otoxic chemotherapeutic agents may benefit patients with high-grade ma lignant brain tumors.