Phase II trial of intravenous lobradimil and carboplatin in childhood brain tumors : a report from the Children's Oncology Group

• Published in: Cancer chemotherapy and pharmacology 2006-09, Vol.58 (3), p.343-347
• Main Authors: WARREN, K, JAKACKI, R, OSBORNE, C, CEHELSKY, J, CALDWELL, D, STANWOOD, J, STEINBERG, S. M, BALIS, F. M, WIDEMANN, B, AIKIN, A, LIBUCHA, M, PACKER, R, VEZINA, G, REAMAN, G, SHAW, D, KRAILO, M
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Blood-Brain Barrier - metabolism; Bradykinin - administration & dosage; Bradykinin - adverse effects; Bradykinin - analogs & derivatives; Bradykinin - therapeutic use; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Carboplatin - administration & dosage; Carboplatin - adverse effects; Carboplatin - therapeutic use; Child; Child, Preschool; Cohort Studies; Drug Administration Schedule; Humans; Infusions, Intravenous; Medical sciences; Neurology; Pharmacology. Drug treatments; Treatment Outcome; Tumors of the nervous system. Phacomatoses
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-005-0172-7

[corrected] Lobradimil is a synthetic bradykinin analog that rapidly and transiently increases the permeability of the blood-brain barrier (BBB). The combination of lobradimil and carboplatin was studied in pediatric patients with primary brain tumors in a phase II trial, the primary endpoints of which were to estimate the response rate and time to disease progression. Patients were stratified by histology into five cohorts: brainstem glioma, high-grade glioma, low-grade glioma, medullobastoma/primitive neuroectodermal tumor (PNET), and ependymoma. Patients received carboplatin adaptively dosed to achieve a target AUC of 3.5 mg min/ml per day (7 mg.min/ml/cycle) intravenously over 15 min on 2 consecutive days and lobradimil 600 ng/kg ideal body weight/day on 2 consecutive days each 28 day cycle. Forty-one patients, age 2-19 years, were enrolled; 38 patients, including 1 patient ultimately determined to have atypical neurocytoma, were evaluable for response. No objective responses were observed in the brainstem glioma (n=12) and high-grade glioma (n = 9) cohorts, although two patients with high-grade glioma had prolonged disease stabilization (>6 months). The study was closed for commercial reasons prior to achieving the accrual goals for the ependymoma (n = 8), medulloblastoma/PNET (n = 6) and low-grade glioma (n = 2) cohorts, although responses were observed in 1 patient with PNET and 2 patients with ependymoma. The combination of lobradimil and carboplatin was inactive in childhood high-grade gliomas and brainstem gliomas.