Phase II trial of intravenous lobradimil and carboplatin in childhood brain tumors: a report from the Children's Oncology Group
- Cancer Chemother Pharmacol. 2006 Sep;58(3):343-7. doi: 10.1007/s00280-005-0172-7.
- 1. National Cancer Institute/Neuro-Oncology Branch, Bethesda, MD 20892-8200, USA. [email protected]
Background: [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 and methods: 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.
Results: 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.
Conclusion: The combination of lobradimil and carboplatin was inactive in childhood high-grade gliomas and brainstem gliomas.
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Cat. No.Product NameDescriptionTargetResearch Area
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target: Bradykinin ReceptorResearch Areas: Cancer