The MGMT level in tumor tissue specimens may be a predictive marker of survival in patients with malignant astrocytoma that is independent of other previously described prognostic variables.

Aims To determine the efficacy of MGMT depletion plus BCNU (carmustine) therapy and the impact of methylation status in adults with glioblastoma (GBM) and gliosarcoma. Methods Methylation analysis was performed on GBM patients with adequate tissue samples. Patients with newly-diagnosed GBM or gliosarcoma were eligible for this Phase III open-label clinical trial. At registration patients were randomized to Arm 1: O6-BG + BCNU (reduced dose) plus radiation therapy (RT) or Arm 2: BCNU plus radiation therapy. Results One hundred eighty-three patients with newly diagnosed GBM or gliosarcoma were enrolled from 42 United States institutions; 90 eligible patients received O6-BG + BCNU plus radiation therapy (RT), and 89 received BCNU plus RT. The trial was halted at first interim analysis per stopping guidelines due to futility (less than 40% improvement on O6BG + BCNU arm). Following adjustment for stratification factors, there was no significant difference in overall (OS) or progression-free survival (PFS) between the two groups (one sided p=0.94 and p=0.88 respectively). Median OS was 11 months (95% c.i. 8 – 13 months) for patients on the O6BG+BCNU arm and 10 months (95% c.i. 8 – 12) for the BCNU arm. PFS was 4 months for patients in each arm. Adverse events were reported in both arms, with significantly more grade 4 and 5 events in the experimental arm. Conclusions The addition of O6-BG to the standard regimen of radiation and BCNU for treatment of newly-diagnosed glioblastoma and gliosarcoma did not offer added benefit and in fact caused additional toxicity.

Patients with GCA were more likely than age- and gender-matched controls to die within the first 5 years following diagnosis.

Although the role of tonsillectomy in managing poststreptococcal uveitis is unknown, our results suggest a positive impact independent of the baseline tonsillitis frequency. Otolaryngologists should be aware of these uncommon sequelae of streptococcal infection and the potential role of tonsillectomy in treatment.

A total of 38 patients with metastatic melanoma received monthly chemotherapy with cisplatin at a dose of 200 mg/m2, per cycle; 14 received 20 mg/m2 cisplatin i.v. on days 1-5 and 24 were given 100 mg/m2 i.v. on days 1 and 8. Objective responses were seen in 2/14 treated on days 1-5 and in 5 of 22 evaluable subjects receiving cisplatin on days 1 and 8, for an overall response rate of 22%. The median survival of all patients was 6 months, with no significant difference observed between the two schedules. Severe neurotoxicity and myelosuppression were more common in patients treated on days 1-5. Two patients treated in this manner were bedridden due to neurotoxicity and four developed grade 4 leukopenia after the first cycle of chemotherapy. Only one patient treated with the divided-dose schedule became leukopenic during the first cycle, and none of the patients were debilitated by neurotoxicity. Thrombocytopenia was statistically more severe. Nausea and vomiting, fatigue, ototoxicity, and paresthesia were seen with equal frequency. Very high doses of cisplatin can be delivered with acceptable toxicity using a divided-dose schedule. As the response rate on this schedule appeared to be comparable with that achieved on the more toxic consecutive 5-day schedule, the former deserves to be tested in diseases known to show a dose response to cisplatin. However, in melanoma, administration of 200 mg/m2 per course did not appear to be associated with a markedly improved response rate, compared with cisplatin alone at "standard" doses.