The use of
chemotherapy has led to improved treatment outcome for some pediatric patients with
medulloblastoma. We have used a pre-radiation
chemotherapy regimen consisting of
vincristine and CDDP. The 9L
gliosarcoma implanted intracranially and subcutaneously in the same animals was used as a preclinical model system to assess the efficacy of treatment combinations including:
vincristine, CDDP, cyclo-
phosphamide,
etanidazole and radiation. The experimental endpoints were percent increase-in-lifespan,
tumor growth delay and
tumor cell survival. Both the
tumor growth delay and percent increase-in-lifespan improved as the number of agents included in the
chemotherapy regimen increased. so that the
chemotherapy regimen including all four agents (ETA/VIN/CDDP/CTX) resulted in the greatest
tumor growth delay (23.6 +/- 1.5 days) and the greatest increase-in-lifespan (35.8%). When radiation (20 Gray, single dose) was added to the treatment regimens the combinations of ETA/CTX/X-ray and ETA/VIN/CDDP/CTX/X-ray resulted in equivalent
tumor growth delays (25.2 +/- 1.3 days and 25.8 +/- 1.7 days, respectively), while the greatest increase-in-lifespan (39.1%) was obtained with the five agent combination. The response of the 9L
gliosarcoma to CDDP and
cyclophosphamide over a dosage range was very similar to that of the murine FSaII
fibrosarcoma. Our results indicate that
etanidazole may be an effective chemosensitizer of
combination chemotherapy and combined modality treatment regimens for
brain tumors.