Affiliation at the time of substantial contribution.
A phase II trial of a multi-agent oral antiangiogenic (metronomic) regimen in children with recurrent or progressive cancer
Version of Record online: 4 OCT 2013
© 2013 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Pediatric Blood & Cancer
Volume 61, Issue 4, pages 636–642, April 2014
How to Cite
Robison, N. J., Campigotto, F., Chi, S. N., Manley, P. E., Turner, C. D., Zimmerman, M. A., Chordas, C. A., Werger, A. M., Allen, J. C., Goldman, S., Rubin, J. B., Isakoff, M. S., Pan, W. J., Khatib, Z. A., Comito, M. A., Bendel, A. E., Pietrantonio, J. B., Kondrat, L., Hubbs, S. M., Neuberg, D. S. and Kieran, M. W. (2014), A phase II trial of a multi-agent oral antiangiogenic (metronomic) regimen in children with recurrent or progressive cancer. Pediatr. Blood Cancer, 61: 636–642. doi: 10.1002/pbc.24794
Conflict of interest: Nothing to declare.
Prior presentation: Preliminary data from this study were presented in part at the 43rd Congress of the International Society of Pediatric Oncology, October 26–30, 2011, Auckland, New Zealand and at the 15th International Symposium on Pediatric Neuro-Oncology, June 24–27, 2012, Toronto, Canada.
- Issue online: 6 FEB 2014
- Version of Record online: 4 OCT 2013
- Manuscript Accepted: 4 SEP 2013
- Manuscript Received: 13 JUN 2013
- Alex's Lemonade Stand Foundation for Childhood Cancer
- Stop & Shop Pediatric Brain Tumor Research Fund
- Pediatric Brain Tumor Research and Clinical Fund Support for data management was provided by Celgene Pharmaceutical Corporation
- drug resistance;
- pediatric oncology;
- phase II clinical trials
Preclinical models show that an antiangiogenic regimen at low-dose daily (metronomic) dosing may be effective against chemotherapy-resistant tumors. We undertook a prospective, open-label, single-arm, multi-institutional phase II study to evaluate the efficacy of a “5-drug” oral regimen in children with recurrent or progressive cancer.
Patients ≤21 years old with recurrent or progressive tumors were eligible. Treatment consisted of continuous oral celecoxib, thalidomide, and fenofibrate, with alternating 21-day cycles of low-dose cyclophosphamide and etoposide. Primary endpoint was to assess, within eight disease strata, activity of the 5-drug regimen over 27 weeks. Blood and urine angiogenesis markers were assessed.
One hundred one patients were enrolled; 97 began treatment. Median age was 10 years (range: 191 days–21 years); 47 (49%) were female. Disease strata included high-grade glioma (HGG, 21 patients), ependymoma (19), low-grade glioma (LGG, 12), bone tumors (12), medulloblastoma/primitive neuroectodermal tumor (PNET, 8), leukemia (4), neuroblastoma (3), and miscellaneous tumors (18). Treatment was generally well tolerated; most common toxicities were hematologic. Twenty-four (25%) patients completed 27 weeks therapy without progression, including HGG: 1 (5%), ependymoma: 7 (37%), LGG: 7 (58%), medulloblastoma/PNET: 1, neuroblastoma: 1, and miscellaneous tumors: 7 (39%). Best response was complete response (one patient with medulloblastoma), partial response (12), stable disease (36), progressive disease (47), and inevaluable (1). Baseline serum thrombospondin levels were significantly higher in patients successfully completing therapy than in those who progressed (P = 0.009).
The 5-drug regimen was well tolerated. Clinical activity was demonstrated in some but not all tumor strata. Pediatric Blood Cancer 2014;61:636–642. © 2013 The Authors Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.