A phase I trial of a new recombinant human β-interferon (BG9015) for the treatment of patients with recurrent gliomas

Primary brain tumors represent an important cause of cancer-related morbidity and mortality in the United States. Despite advances in neurosurgery and radiotherapy, the median survival of patients with malignant gliomas remains less than 1 year. A contributing factor to the poor prognoses of these patients is the diffuse, infiltrative nature of these tumors, which limits the effectiveness of focal therapies (i.e. surgery and radiation). Unfortunately, standard chemotherapy has been of limited benefit in the treatment of malignant gliomas, underlying the necessity for new drugs with novel mechanisms of action. On the basis of promising in vitro and clinical data demonstrating significant antiglioma activity of purified IFN-β and a synthetic IFN-β (Betaseron), we conducted a Phase I trial of a new, nonmutated, glycosylated recombinant human IFN-β (BG9015) in patients with recurrent, high-grade astrocytomas. In this trial, we demonstrate that the maximally tolerated dose of BG9015 is 6 million units/m² delivered by intramuscular injection three times per week. Dose-limiting neurotoxicity was seen in both patients treated at 8 million units/m². Additionally, we demonstrate that high BG9015 serum levels are associated with a fall in natural killer cell number, radiographic response, and prolonged survival. We conclude that BG9015 has activity in patients with malignant gliomas, although the therapeutic index may be narrow. Future studies will be needed to confirm the observation that natural killer cell number and activity as well as BG9015 serum levels are important markers of antitumor activity.