Edward J. Dropcho

Steroid-induced weakness in patients with primary brain tumors.

Clinically significant steroid myopathy (SM) occurred in 23 (10.6%) of 216 adult patients with primary brain tumors who received 2 or more continuous weeks of daily dexamethasone therapy. SM occurred over a wide range of peak and cumulative doses of dexamethasone as well as a wide range of periods of continuous treatment. This was not an entirely random event, however, as two-thirds of the patients developed their weakness during the 9th through the 12th week of continuous dexamethasone treatment. The risk of developing SM was significantly lower in patients taking phenytoin than in patients who were not taking anticonvulsants. The only other patient or treatment factor associated with SM was a possible direct correlation with the appearance of a cushingoid body habitus. In this retrospective review, the occurrence of SM had a significant negative impact on the quality of life of all affected individuals. As expected, patients who tolerated a reduction in their steroid dose improved, while other patients suffered the combined effects of tumor progression and worsening myopathy. Substituting a nonfluorinated glucocorticoid for dexamethasone is probably advisable if neuro-oncology patients affected by SM cannot be weaned from the steroids.

Antineuronal (anti-Ri) antibodies in a patient with steroid-responsive opsoclonus-myoclonus.

A 45-year-old woman developed opsoclonus, myoclonus, and severe truncal and gait ataxia. Serum and CSF contained IgG antibodies that appear to be identical to “anti-Ri” antibodies associated with paraneoplastic opsoclonus and ataxia. The patient had a fluctuating course with exacerbations that responded well to corticosteroids and later to cyclophosphamide. Her anti-Ri antibody titer has declined significantly but still remains high. After more than 3 years of follow-up, no neoplasm has been detected.

Neurotoxicity of Cancer Chemotherapy

Neurological dysfunction is a common side effect of many chemotherapy drugs. For several agents neurotoxicity is common, severe, and can be dose-limiting. This is a review of the clinical features of chemotherapy-induced syndromes involving the central and peripheral nervous systems.

A phase III randomized prospective trial of external beam radiotherapy, mitomycin C, carmustine, and 6-mercaptopurine for the treatment of adults with anaplastic glioma of the brain

PURPOSE This study was designed to evaluate strategies to overcome the resistance of anaplastic gliomas of the brain to external beam radiotherapy (ERT) plus carmustine (BCNU). Patients were > or = 15 years of age, had a histologic diagnosis of malignant glioma, and a Karnofsky performance status (KPS) > or = 60%. METHODS AND MATERIALS In Randomization 1, patients were assigned to receive either ERT alone (61.2 Gy) or ERT plus mitomycin C (Mito, IV 12.5 mg/m(2)) during the first and fourth week of ERT. After this treatment, patients went on to Randomization 2, where they were assigned to receive either BCNU (i.v. 200 mg/m(2)) given at 6-week intervals or 6-mercaptopurine (6- MP, 750 mg/m(2) IV daily for 3 days every six weeks), with BCNU given on the third day of the 6-MP treatment. Three hundred twenty-seven patients underwent Randomization 1. One hundred sixty-four received ERT alone, and 163 received ERT + Mito [average 52.7 years; 63% male; 69% glioblastoma multiforme (GBM); 66% had a resection; 56% KPS > or = 90%]. Step-wise analysis of survival from Randomization 1 or 2 indicates that survival was significantly diminished by: (a) age > or = 45 years (b) KPS < 90%; (c) GBM/gliosarcoma histology; (d) stereotactic biopsy as opposed to open biopsy or resection. Median survival from Randomization 1 in both arms (ERT + Mito) was 10.8 months. Median survival from Randomization 2 was 9.3 months for BCNU/6MP vs. 11.4 months for the BCNU group (p = 0.35). Carmustine/6-MP showed a possible survival benefit for histologies other than GBM/GS. Two hundred and thirty-three patients underwent Randomization 2. The proportion of patients in the ERT group who terminated study prior to Randomization 2 was significantly less in the ERT group than in the ERT + Mito group (20 vs. 37%, p < 0.001). CONCLUSIONS (a) The addition of Mito to ERT had no impact on survival; (b) patients treated with ERT + Mito were at greater risk of terminating therapy prior to Randomization 2; (c) there was not a significant survival benefit to the addition of 6-MP to BCNU.

Randomized comparison of diaziquone and carmustine in the treatment of adults with anaplastic glioma.

PURPOSE We conducted a phase III trial comparing intravenous (IV) diaziquone (AZQ) and carmustine (BCNU) as single agents in patients with cerebral anaplastic gliomas who had received surgery and radiotherapy. Its purpose was to compare the efficacy of AZQ with that of BCNU, the standard agent for brain tumor chemotherapy. PATIENTS AND METHODS Randomization between the two regimens occurred 8 weeks after completion of radiotherapy. A total of 251 patients were randomized to receive either AZQ or BCNU, and there were no significant differences between the two treatment arms in any of the known prognostic variables, including age, histologic grade, and Karnofsky performance status (KPS). RESULTS There was no significant difference in either time to tumor progression or survival between the two treatment arms. Age and histology were strong predictors of outcome, whereas KPS had relatively less effect. Three groups of patients with distinctly different outcomes could be identified: (1) older age (45+) and glioblastoma/gliosarcoma (GBM/GS) patients had a median survival of 37 weeks after randomization; (2) patients with either older age or GBM/GS had a median survival of 61 weeks; and (3) younger age (< 45) and non-GBM/GS (usually anaplastic astrocytoma) patients had a median survival of 147 weeks. Toxicity was primarily hematologic, although acute gastrointestinal toxicity and chronic pulmonary toxicity were more common with BCNU. Patients randomized to AZQ who had significant hematologic toxicity that required dose reduction after the first treatment cycle had significantly longer time to tumor progression and survival than those who did not require dose reduction (P = .011 and .016, respectively). CONCLUSION There was no significant difference in efficacy between AZQ and BCNU in patients with anaplastic gliomas as tested in this study, although AZQ was somewhat better tolerated.