Treatment of recurrent malignant supratentorial astrocytomas with carboplatin and etoposide combined with recombinant mutant human tumor necrosis factor-alpha.

BACKGROUND

This study assesses the safety, tolerance and preliminary efficacy of combined treatment with carboplatin, etoposide and recombinant human mutant tumor necrosis factor-alpha (TNF-SAM2) for recurrent malignant supratentorial astrocytomas at first relapse.

MATERIALS AND

METHODS

Carboplatin was administered intravenously at a dose of 400 mg/m2 on Day 1, while etoposide was administered intravenously at a dose of 100 mg/m2 from Day 1 to Day 3 for 3 days. From Day 7, 80x10(4) U/m2 TNF-SAM2 was given intravenously for up to 5 injections for 2 weeks. Treatment was repeated every 8 to 12 weeks.

RESULTS

Ten patients previously treated with surgery, radiation therapy and chemotherapy with a nitrosourea (ranimustine: MCNU) for malignant astrocytomas received this regimen for up to four cycles. Three patients with anaplastic astrocytomas, one patient with anaplastic oligoastrocytoma and 6 patients with glioblastomas (3 men and 7 women), aged 27 to 69 years, were eligible and were evaluated for response and toxicity. Grade 2 and 3 hematological toxicities occurred in 4 (40%) and 2 patients (20%), respectively. Grade 2 hepatic toxicity was observed in two patients. Of 9 evaluable patients, three (33%), including one glioblastoma, partially responded to the treatment (PR) with time to tumor progression (TTP) of 231, 121 and 57 weeks, respectively. Two patients had stable disease (SD), while 4 glioblastomas (44%) had progressive disease (PD) with TTP values of 11, 15, 6 and 12 weeks, respectively.

CONCLUSION

These results suggest that combined therapy with carboplatin, etoposide and recombinant mutant TNF-alpha in this patient population seems to be safe and acceptable and may benefit those with recurrent anaplastic astrocytomas. These intriguing clinical observations warrant a properly stratified randomized trial to determine whether this approach can provide therapeutic benefits and improve survival.