Treatment of malignant astrocytomas with recombinant mutant human tumor necrosis factor-alpha (TNF-SAM2)

We present our experience with a combination chemotherapy regimen consisting of ranimustine (MCNU) and recombinant human mutant tumor necrosis factor-alpha (TNF-SAM2) for malignant astrocytomas. The initial regimens were prescribed as adjuvant therapy in conjunction with radiotherapy following standard surgical treatment. Newly diagnosed patients were treated with up to four cycles of this regimen (TNF-SAM2, MCNU, and radiotherapy: TMR group). Seventeen patients (11 men and 6 women) aged 24 to 68 years (median 54.6 years) were eligible and evaluated for response and toxicity. The estimated median survival time was 354 weeks with anaplastic astrocytomas, and 76 weeks with glioblastomas. One- and 2-year survival rates were 100% and 100% with anaplastic astrocytomas, and 69.2% and 29.7% with glioblastomas. Grade 3 and 4 hematological toxicities were not experienced. None of the patients experienced a treatment delay due to toxicity. All other acute toxicities were anticipated and manageable. Twenty three patients (11 men and 12 women) aged 22 to 66 years (median 50.7 years) were evaluated as a historical control of patients who received chemotherapy with MCNU alone in conjunction with radiotherapy following standard surgical treatment (MCNU and radiotherapy: MR group). The estimated median survival time was 205 weeks with anaplastic astrocytomas, and 62 weeks with glioblastomas. One- and 2-year survival rates were 88.9% and 66.7% with anaplastic astrocytomas, and 71.4% and 7.1% with glioblastomas in this group. There were no significant differences in survival rates between patients in the TMR and MR groups with either anaplastic astrocytoma or glioblastoma. However, despite the small number of patients, those with anaplastic astrocytoma in the TMR group tended to survive longer than those in the MR group. These results suggest that combined chemotherapy with mutant TNF-alpha may benefit those with anaplastic astrocytoma, and thus warrants further evaluation. On the other hand, the lack of activity does not warrant any further study of this schedule of TNF-SAM2 for the treatment of glioblastoma.