Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Cancer chemotherapy and pharmacology, 2006-09, Vol.58 (3), p.343-347

Ort / Verlag

Berlin: Springer

Erscheinungsjahr

2006

Quelle

MEDLINE

Beschreibungen/Notizen

• [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.