Richard L. Rovit, W. Kemp Clark, Arthur B. Eisenbrey, Louis Finney, William E. Hunt, Byron C. Pevehouse and Walter W. Whisler
A cooperative clinical trial
Michael D. Walker, Eben Alexander Jr., William E. Hunt, Collin S. MacCarty, M. Stephen Mahaley Jr., John Mealey Jr., Horace A. Norrell, Guy Owens, Joseph Ransohoff, Charles B. Wilson, Edmund A. Gehan and Thomas A. Strike
✓ A controlled, prospective, randomized study evaluated the use of 1,3-bis(2-chloroethyl)-l-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.
Michael D. Walker, Eben Alexander Jr., William E. Hunt, Carl M. Leventhal, M. Stephen Mahaley Jr., John Mealey, Horace A. Norrell, Guy Owens, Joseph Ransohoff, Charles B. Wilson and Edmund A. Gehan
✓ A controlled, prospective, randomized study evaluated the use of mithramycin in the treatment of anaplastic glioma compared to a similar group of patients receiving best conventional care. From a total of 116 patients in the study, 96 were within the valid study group. All patients were operated on, had histological confirmation of anaplastic glioma, and received radiotherapy at the discretion of the principal investigator. Fifty-two patients received mithramycin at a dose of 25 µg/kg/day for 21 days, while 44 patients were in the control group. There was no significant difference in the median survival from time of randomization in those receiving mithramycin (21 weeks) as compared to those not receiving mithramycin (26 weeks). There was no significant difference between the two groups in relation to age distribution, sex, location, diagnosis, tumor characteristics, signs or symptoms, or radiotherapy received. Duration of symptoms correlates positively with survival and was also significantly longer in the control group than in the treated group. This, however, did not account for the failure of mithramycin to be found an effective agent. Although the study was not designed to evaluate the efficacy of radiotherapy, patients who were so treated had a significant improvement in survival. The toxic complications of mithramycin included gastrointestinal symptoms, dermatological involvement, anemia, and liver dysfunction, indicating the need for close supervision.
Results of the National Acute Spinal Cord Injury Study
Michael B. Bracken, Mary Jo Shepard, Karen G. Hellenbrand, William F. Collins, Linda S. Leo, Daniel F. Freeman, Franklin C. Wagner, Eugene S. Flamm, Howard M. Eisenberg, Joseph H. Goodman, Phanor L. Perot Jr., Barth A. Green, Robert G. Grossman, John N. Meagher, Wise Young, Boguslav Fischer, Guy L. Clifton, William E. Hunt and Nathan Rifkinson
✓ A multi-center double-blind randomized clinical trial was conducted by the National Acute Spinal Cord Injury Study Group to examine the efficacy of high-dose methylprednisolone (1000-mg bolus and 1000 mg daily thereafter for 10 days) compared with that of a standard dose (100-mg bolus and 100 mg daily for 10 days). No significant difference was observed in neurological recovery of motor function, pinprick response, or touch sensation 1 year after injury between the two treatment groups, after adjustment for other potentially confounding factors. Analyses that specifically took into account the patients' total steroid dose and relative weight confirmed the lack of a steroid treatment effect. The case fatality rate was 10.7% during the 1st year after injury, and this was not associated with the steroid treatment protocol or the patient's gender. Deaths did occur significantly more frequently among patients who were completely (15.3%) and partially (8.6%) plegic than among those who were paretic (2.5%, p = 0.0005), and among patients aged 50 years or older (38.6%, p = 0.0001).