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A phase II trial of a multi‐agent oral antiangiogenic (metronomic) regimen in children with recurrent or progressive cancer
Author(s) -
Robison Nathan J.,
Campigotto Federico,
Chi Susan N.,
Manley Peter E.,
Turner Christopher D.,
Zimmerman Mary Ann,
Chordas Christine A.,
Werger Annette M.,
Allen Jeffrey C.,
Goldman Stewart,
Rubin Joshua B.,
Isakoff Michael S.,
Pan Wilbur J.,
Khatib Ziad A.,
Comito Melanie A.,
Bendel Anne E.,
Pietrantonio Jay B.,
Kondrat Laura,
Hubbs Shan M.,
Neuberg Donna S.,
Kieran Mark W.
Publication year - 2014
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.24794
Subject(s) - medicine , regimen , oncology , blood cancer , cancer
Background 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. Procedure 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. Results 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). Conclusion 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.