Phase I analysis of systemic interferon alpha utilized with gliadel in adults with recurrent glioblastoma multiforme (GBM)

Abstract

11508 Background: Local therapy with Gliadel was found to increases median survival at recurrence from 23 to 31 weeks when compared to placebo wafers. Brain tumor specimens have been observed to have a 40–50% rate of deletion of the IFNα interferon a gene. Previous clinical studies have demonstrated response rates to IFN-α in the range of 0–41% in the treatment of recurrent primary malignant glioma, either alone, or in combination with other modalities. This study assess the safety and toxicity of Interferon α-2b (IFN-α) and 3.85% BCNU-permeated wafers (Gliadel®). Methods: This is a phase I dose escalation assessment of the toxicity of IFN-α utilized in conjunction with Gliadel® in patients with recurrent GBM, who failed previous radiation and chemotherapy. Ten patients were enrolled in this dose escalation trial. Three dose levels were studied were with the starting dosage of was IFN-α 3 Mu/m2 (n = 3), 6 Mu/m2 (n = 3) and 9 Mu/m2 (n = 4) subcutaneously injection 3 times a week for a total period of 8 weeks with the first dose being initiated 1 week following craniotomy and Gliadel placement. Results: There were 10 patients, 5 males and 5 females with a median age of 46 yrs (range 35–55). At re-operation, all histology revealed 10 GBM. At dose 3 Mu/m2, 2/3 pts developed grade 2 fatigue, myalgia and depression, but completed treatment with 1 PR (109 + wks) and 1 CR (91 + wks) and 1 PD (6 wks). Another patient was off study because of progressive disease (PD). At dose 6 Mu/m2, all 3 had PD with 2 pts having Grade 2 received a dose reduction because of diarrhea and 1 patient withdrawing early for PD finished only 1 cycle (4 wks). At dose 9 Mu/m2, 2 patients developed grade 3 toxicity fatigue/malaise and one patient completed therapy with dose reduction and but progressed, another patient stopped treatment after first 3 doses due to progression. There were overall response of 20% (1 PR and 1 CR) with duration of 109+ and 91+ wks. Clinical response with IFNα gene is being analyzed. Conclusions: This study defined MTD at 6 Mu/m2 with a DLT at 9 Mu/m2 and recommended a Phase II dose in this population. Since interestingly, the responses occurred at the lowest dose, suggesting a portion of the effect may be anti-angiogenic in nature. No significant financial relationships to disclose.