Phase II studies of RMP-7 and carboplatin in the treatment of recurrent high grade glioma

The selective bradykinin analogue, RMP-7, transiently increases the permeab ility of the blood brain barrier and the delivery of hydrophilic agents int o brain tumours. In 87 recurrent glioma patients (WHO Grade III/IV, median age 46, Karnofsky 70%) clinical and Magnetic Resonance Imaging (MRI) respon ses to i.v. cycles (q 28 days) of RMP-7 (300 ng/kg given as a 10 min infusi on) and carboplatin (AUC 4-9) were assessed. 45 of these patients were chem otherapy naive (CN-RMP) and 42 had received one prior course of chemotherap y (CP-RMP). Neurological impairment, performance status and steroid use wer e measured prior to dosing at each cycle and tumour volume by 3-D MRI at th e end of cycles 2, 4, 6, 9 and 12. Clinical evaluation of response demonstr ated that 61% of CN-RMP patients were either stable or improved whilst this was 39% for CP-RMP patients, of which 37% and 8% improved respectively. Ra diological evaluation showed 79% of CN-RMP patients were either stable, par tial or complete responses and 24% for CP-RMP patients, of which 32% and 5% were CR or PR respectively. The median duration of response was 30.3 weeks in CN-RMP patients and 19.6 weeks in the CP-RMP group. Lack of response was associated with substantial baseline tumour volume. Drug toxicity was as previously reported for carbo platin. 11 patients had treatment-associated transient focal seizures. Thes e results indicate that RMP-7 and carboplatin have significant activity in recurrent malignant glioma following radiotherapy.