title: Phase II studies of RMP-7 and carboplatin in the treatment of recurrent high grade glioma. RMP-7 European Study Group.
abstract: The selective bradykinin analogue, RMP-7, transiently increases the permeability of the blood brain barrier and the delivery of hydrophilic agents into brain tumours. In 87 recurrent glioma patients (WHO Grade III/IV, median age 46, Karnofsky 70%) clinical and Magnetic Resonance Imaging (MRI) responses to i.v. cycles (q 28 days) of RMP-7 (300 ng/kg given as a 10 min infusion) and carboplatin (AUC 4-9) were assessed. 45 of these patients were chemotherapy naive (CN-RMP) and 42 had received one prior course of chemotherapy (CP-RMP). Neurological impairment, performance status and steroid use were measured prior to dosing at each cycle and tumour volume by 3-D MRI at the end of cycles 2, 4, 6, 9 and 12. Clinical evaluation of response demonstrated 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. Radiological evaluation showed 79% of CN-RMP patients were either stable, partial 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 carboplatin. 11 patients had treatment-associated transient focal seizures. These results indicate that RMP-7 and carboplatin have significant activity in recurrent malignant glioma following radiotherapy.
authors.affiliation: Department of Clinical Oncology, University of Edinburgh, Western General Hospital, UK.
authors.forename: A
authors.initials: A
authors.lastname: Gregor
authors.forename: M
authors.initials: M
authors.lastname: Lind
authors.forename: H
authors.initials: H
authors.lastname: Newman
authors.forename: R
authors.initials: R
authors.lastname: Grant
authors.forename: D M
authors.initials: DM
authors.lastname: Hadley
authors.forename: T
authors.initials: T
authors.lastname: Barton
authors.forename: C
authors.initials: C
authors.lastname: Osborn
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001920:Bradykinin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology*; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use*; D005910:Glioma / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: C089876:RMP 7; D016190:Carboplatin; D001920:Bradykinin