A phase II trial of a multi-agent oral antiangiogenic (metronomic) regimen in children with recurrent or progressive cancer
| Autor: | Christine Chordas, Michael S. Isakoff, Laura Kondrat, Ziad Khatib, Anne Bendel, Shannon M. Hubbs, Peter E. Manley, Joshua B. Rubin, Federico Campigotto, Wilbur J. Pan, Mark W. Kieran, Stewart Goldman, Donna Neuberg, Christopher D. Turner, Jeffrey C. Allen, Annette M. Werger, Mary Ann Zimmerman, Melanie Comito, Jay B. Pietrantonio, Susan N. Chi, Nathan Robison |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Oncology
Male Phases of clinical research Angiogenesis Inhibitors angiogenesis Fenofibrate Neoplasms Antineoplastic Combined Chemotherapy Protocols Medicine Prospective Studies Prospective cohort study Child Etoposide Research Articles Sulfonamides Neovascularization Pathologic Hematology pediatric oncology Prognosis Thalidomide Survival Rate Child Preschool Female medicine.drug Adult medicine.medical_specialty Cyclophosphamide Adolescent Young Adult Internal medicine Humans Dosing Neoplasm Staging drug resistance business.industry Cancer Infant medicine.disease phase II clinical trials Surgery Regimen Celecoxib Pediatrics Perinatology and Child Health Pyrazoles Neoplasm Recurrence Local business Follow-Up Studies |
| Zdroj: | Pediatric Blood & Cancer |
| ISSN: | 1545-5017 1545-5009 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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