A controlled, prospective, randomized study evaluated the use of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and/or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma. A total of 303 patients were randomized into this study, of whom 222 (73%) were within the Valid Study Group (VSG), having met the protocol criteria of neuropathology, corticosteroid control, and therapeutic approach. Patients were divided into four random groups, and received BCNU (80 mg/sq m/day on 3 successive days every 6 to 8 weeks), and/or radiotherapy (5000 to 6000 rads to the whole brain through bilateral opposing ports), or best conventional care but no chemotherapy or radiotherapy. Analysis was performed on all patients who received any amount of therapy (VSG) and on the Adequately Treated Group (ATG), who had received 5000 or more rads radiotherapy, two or more courses of chemotherapy, and had a minimum survival of 8 or more weeks (the interval that would have been required to have received either the radiotherapy or chemotherapy). Median survival of patients in the VSG was, best conventional care: 14 weeks (ATG: 17.0 weeks); BCNU: 18.5 weeks (ATG: 25.0 weeks); radiotherapy: 35 weeks (ATG: 37.5 weeks); and BCNU plus radiotherapy: 34.5 weeks (ATG: 40.5 weeks). All therapeutic modalities showed some statistical superiority compared to best conventional care. There was no significant difference between the four groups in relation to age distribution, sex, location of tumor, diagnosis, tumor characteristics, signs or symptoms, or the amount of corticosteroid used. An analysis of prognostic factors indicates that the initial performance status (Karnofsky rating), age, the use of only a surgical biopsy, parietal location, the presence of seizures, or the involvement of cranial nerves II, III, IV, and VI are all of significance. Toxicity included acceptable, reversible thrombocytopenia and leukopenia.

Within three weeks of definitive surgical intervention, 467 patients with histologically proved malignant glioma were randomized to receive one of four treatment regimens: semustine (MeCCNU), radiotherapy, carmustine (BCNU) plus radiotherapy, or semustine plus radiotherapy. We analyzed the data for the total randomized population and for the 358 patients in whom the initial protocol specifications were met (the valid study group). Observed toxicity included acceptable skin reactions secondary to radiotherapy and reversible leukopenia and thrombocytopenia due to chemotherapy. Radiotherapy used alone or in combination with a nitrosourea significantly improved survival in comparison with semustine alone. The group receiving carmustine plus radiotherapy had the best survival, but the difference in survival between the groups receiving carmustine plus radiotherapy and semustine plus radiotherapy was not statistically significant. The combination of carmustine plus radiotherapy produced a modest benefit in long-term (18-month) survival as compared with radiotherapy alone, although the difference between survival curves was not significiant at the 0.05 level. This study suggests that it is best to use radiotherapy in the post-surgical treatment of malignant glioma and to continue the search for an effective chemotherapeutic regimen to use in addition to radiotherapy.

Within 3 weeks of definitive surgery, 571 adult patients with histologically confirmed, supratentorial malignant gliomas were randomly assigned to receive one of three chemotherapy regimens: BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) alone, alternating courses (every 8 weeks) of BCNU and procarbazine, or BCNU plus hydroxyurea alternating with procarbazine plus VM-26 (epipodophyllotoxin). Patients accrued in 1980 and 1981 were to receive 6020 rads of whole-brain radiotherapy concurrent with the first course of chemotherapy. Patients accrued in 1982 and 1983 were randomly assigned to receive either whole-brain irradiation as above, or 4300 rads of whole-brain radiotherapy plus 1720 rads coned down to to the tumor volume. The data were analyzed for the total randomized population and separately for the 510 patients, termed the "Valid Study Group (VSG)," who met protocol eligibility specifications (including central pathology review), 80% of whom had glioblastoma multiforme. The median survival times from time of randomization for the three chemotherapy groups of the VSG ranged from 11.3 to 13.8 months, and 29% to 37% of the patients survived for 18 months (life-table estimate); the differences between these groups were not statistically significant. Survival differences between the radiotherapy groups were small and not statistically significant. It is concluded that, for malignant glioma, giving part of the radiotherapy by coned-down boost is as effective as full whole-brain irradiation, and that multiple-drug chemotherapy as outlined in this protocol conferred no significant survival advantage over BCNU alone.

This series of 228 patients with infantile non-neoplastic hydrocephalus who received either a ventriculoatrial (VA) or a ventriculoperitoneal (VP) shunt before 2 years of age was followed for an average of 7 years, and the results with the two types of shunt were compared. Mortality and infection rates were similar for both groups of patients, but children with VP shunts required significantly fewer revisions and had a much greater likelihood of not having any revisions during the follow-up period. Late complications occurred more frequently with VA shunts and were more serious. It is concluded that VP shunts offer significant advantages over VA systems in this population.

This Phase III trial tested the efficacy and safety of intra-arterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) for the treatment of newly resected malignant glioma, comparing intra-arterial BCNU and intravenous BCNU (200 mg/sq m every 8 weeks), each regimen without or with intravenous 5-fluorouracil (1 gm/sq m three times daily given 2 weeks after BCNU). All patients also received radiation therapy. A total of 505 patients were randomly assigned within the study. Fifty-seven patients were excluded, primarily because of neuropathology error, and the remaining 448 patients constituted the Valid Study Group. Of the total 505 patients, 190 patients could not receive intra-arterial BCNU and 315 patients were randomly assigned to receive intra-arterial (167 patients) and intravenous (148 patients) BCNU. Actuarial analysis (log-rank) demonstrated reduced survival for the intra-arterial group (p = 0.03). Serious toxicity was observed in the intra-arterial group; 16 patients (9.5%) developed irreversible encephalopathy with computerized tomography evidence of cerebral edema, and 26 patients (15.5%) developed visual loss ipsilateral to the infused carotid artery. Administration of 5-fluorouracil did not influence survival. The survival rate between the intravenous and the intra-arterial BCNU patients with glioblastoma multiforme did not differ, but was worse for intra-arterial BCNU patients with anaplastic astrocytoma than for those receiving intravenous BCNU (p = 0.002). Neuropathologically, intra-arterial BCNU produced white matter necrosis. It is concluded that intra-arterial BCNU is neither safe nor effective in prolonging survival when administered by the methods used in this study of newly diagnosed patients with malignant glioma.