Thirty-five patients with primary malignant brain tumor were treated with scheduled combination chemotherapy using Adriamycin and BCNU, CCNU or methyl CCNU after surgical treatment and BAR therapy. Adriamycin (0.8 mg/kg) on the first and second day and 100 mg/m2 of BCNU, CCNU or methyl CCNU on the second or the third day were given. This combination chemotherapy was repeated every two months. The survival rates at 1 and 1.5 year after operation of highly malignant glioma (13 patients : 11 with glioblastoma, 1 with oligodendroblastoma and 1 with medulloblastoma) were 83%, 45% respectively, and for moderately malignant glioma (15: 11 with low grade astrocytoma, 2 with oligodendroglioma and 2 with ependymoma), they were 86%, 78% at 1 and 2 years respectively. The 1 year survival rate of this chemotherapy with BAR therapy is better than that of BAR only in highly malignant glioma. The average survival time of pontine glioma was 13.8 months. The complications were alopecia (49%), nausea and vomiting (46%) and leucocytopenia below 4, 000 (60%). When 0.8 mg/kg of Adriamycin and 100 mg/m2 of BCNU were administered, the sudden leucocyte decrease was frequently observed after days from the administration, whereas 0.4 mg/kg of Adriamycin and 60 mg/m2 of BCNU or methyl CCNU was given, decrease of WBC was moderate.
The minimum duration for the repopulation of treated human glioblastoma may be computed with the knowledge of a cell cycle time of 3 days and growth fraction of 0.3. For one tumor cell to become 100 cells without cell loss, it will take a minimum of 53 days. In this case, chemotherapeutic agents resulting in a 2 log cell kill will be effective. Therefore, in order to obtain a stepwise reduction in tumor mass using agents of 2 log cell kill, a second course of therapy should be administered within 53 days. It is reasonable that the administration of Adriamycin and BCNU or CCNU is repeated every 8 weeks, assuming this combination chemotherapy results in 2 log kill.
