Abstract
Backround: 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.
Original language | English (US) |
---|---|
Pages (from-to) | 343-347 |
Number of pages | 5 |
Journal | Cancer Chemotherapy and Pharmacology |
Volume | 58 |
Issue number | 3 |
DOIs | |
State | Published - Sep 2006 |
Externally published | Yes |
Keywords
- Brain tumors
- Children
- Ependymoma
- Glioma
- Lobradimil
- Medulloblastoma
- Phase II
- RMP-7
ASJC Scopus subject areas
- Oncology
- Toxicology
- Pharmacology
- Cancer Research
- Pharmacology (medical)