Stereotactic injection of DTI-015 into recurrent malignant gliomas: phase I/II trial.

DTI-015 (BCNU in 100% ethanol) utilizes solvent facilitated perfusion for the intratumoral treatment of gliomas. The ethanol solvent vehicle facilitates a rapid and thorough saturation of the tumor with the dissolved anticancer agent BCNU. We conducted a phase I/II dose escalation study of DTI-015 in 40 heavily pretreated patients with inoperable recurrent malignant glioma. The study goals were to establish a maximally tolerated dose (MTD) for DTI-015 and assess its safety and activity. Patients received stereotactic intratumoral injection of DTI-015 under magnetic resonance imaging guidance. Dose escalation was performed in two phases. First, DTI-015 volume was escalated at a set BCNU concentration of 12.5 mg/ml; second, BCNU mg dose was escalated by increasing BCNU concentration to 30, 45, 60, and 75 mg/ml. A MTD of 5 ml and 240 mg was established. Twenty-five of 28 DTI-015 treatments (89%) using </=MTD were administered safely without producing high-grade drug-related adverse events. Median survival for GBM patients administered DTI-015 at </=MTD was 55 weeks. Magnetic resonance imaging demonstrated stable disease in 72% of evaluable patients with a median of 10.5 weeks. The results suggest that DTI-015 administered at </=MTD is well tolerated and active in patients with inoperable recurrent GBM.