Phase II trial of pre-irradiation KRN8602 (MX2) in malignant glioma patients

KRN8602 (MX2) is a newly developed morpholino anthracycline that crosses th e blood-brain barrier where it becomes distributed in brain tissue after in travenous administration. This morpholino anthracycline has been found to b e effective against human glioma cells and the intracerebrally transplanted tumors in vivo. We performed a phase II trial using KRN8602 as a single agent in malignant glioma patients who had not received prior adjuvant therapy. The 13 patients (5 glioblastomas, 7 anaplastic astrocytomas and 1 malignant oligodendroglioma) enrolled received at least 1 cycle of KRN8602 at 35 mg/ m(2)/day in 3-4 week intervals by intravenous bolus. Ten of these patients could be evaluated for response, and 13 for toxicity. Three patients (1 gli oblastoma and 2 anaplastic astrocytomas) demonstrated a complete response ( 3/10, 30%). Concerning side effects, myelosuppression was moderately severe, with 30.7% of patients developing grade 3 leukopenia. Severe nausea/vomiting was obse rved in 69% of the patients, however, cardiotoxicity was not observed. The results indicate that KRN8602 demonstrated modest activity against mali gnant glioma with relatively severe, but manageable toxicity. Further asses sment of the efficacy and toxicity of KRN86O2 against malignant glioma may be worthwhile.