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Pilot study of a pediatric metronomic 4-drug regimen

BACKGROUND: Metronomic chemotherapy (MC) is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. MC is gaining interest as an alternative strategy to fight resistant cancer. OBJECTIVE: to assess the safety of 4 drug M...

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Autores principales: André, Nicolas, Abed, Sylvie, Orbach, Daniel, Alla, Corinne Armari, Padovani, Laetitia, Pasquier, Eddy, Gentet, Jean Claude, Verschuur, Arnauld
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282100/
https://www.ncbi.nlm.nih.gov/pubmed/22156656
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author André, Nicolas
Abed, Sylvie
Orbach, Daniel
Alla, Corinne Armari
Padovani, Laetitia
Pasquier, Eddy
Gentet, Jean Claude
Verschuur, Arnauld
author_facet André, Nicolas
Abed, Sylvie
Orbach, Daniel
Alla, Corinne Armari
Padovani, Laetitia
Pasquier, Eddy
Gentet, Jean Claude
Verschuur, Arnauld
author_sort André, Nicolas
collection PubMed
description BACKGROUND: Metronomic chemotherapy (MC) is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. MC is gaining interest as an alternative strategy to fight resistant cancer. OBJECTIVE: to assess the safety of 4 drug MC regimen in pediatric patients with refractory or relapsing various tumors types. SETTING: From November 2008 to December 2010, in three academic pediatric oncology centers, 16 children (median age 12 years old; range 5.5-20) were included in this pilot study. This treatment was proposed to children with refractory disease for whom no further effective treatments were available. Most frequent diagnosis were medulloblastoma/cerebral PNET (5) osteosarcoma (5), and one case each of nephroblastoma, high grade glioma, Hodgkin lymphoma, rhabdomyosarcoma, neuroblastoma and kidney rhabdoid tumour. The MC regimen consisted in cycles of 56 days (8 weeks) with weekly vinblastine 3 mg/m(2) (week 1-7), daily cyclophosphamide 30 mg/m(2) (days 1-21), and twice weekly methotrexate 10 mg/m(2); (days 21-42), and daily celecoxib 100 mg to 400 mg twice daily (days1-56) followed by a 2-weeks chemotherapy break. Adverse events were determined through laboratory analysis and investigator observations. RESULTS: One objective response was observed in a patient with Hodgkin lymphoma, and 4 patients experienced disease stabilization and continued their treatment for 3 cycles (24 weeks) or more. At last follow-up, 7 patients (43%) are alive including 1 still undergoing treatment. During the overall 36 cycles of treatments received by patients, 4 grade IV toxicities and 24 grade III toxicities were observed in 11 cycles in only 10 different patients. CONCLUSION: The metronomic regimen we report here was well tolerated and associated with disease stabilization. This regimen is currently being evaluated in a national multicenter phase II study.
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spelling pubmed-32821002012-02-22 Pilot study of a pediatric metronomic 4-drug regimen André, Nicolas Abed, Sylvie Orbach, Daniel Alla, Corinne Armari Padovani, Laetitia Pasquier, Eddy Gentet, Jean Claude Verschuur, Arnauld Oncotarget Brief Reports BACKGROUND: Metronomic chemotherapy (MC) is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. MC is gaining interest as an alternative strategy to fight resistant cancer. OBJECTIVE: to assess the safety of 4 drug MC regimen in pediatric patients with refractory or relapsing various tumors types. SETTING: From November 2008 to December 2010, in three academic pediatric oncology centers, 16 children (median age 12 years old; range 5.5-20) were included in this pilot study. This treatment was proposed to children with refractory disease for whom no further effective treatments were available. Most frequent diagnosis were medulloblastoma/cerebral PNET (5) osteosarcoma (5), and one case each of nephroblastoma, high grade glioma, Hodgkin lymphoma, rhabdomyosarcoma, neuroblastoma and kidney rhabdoid tumour. The MC regimen consisted in cycles of 56 days (8 weeks) with weekly vinblastine 3 mg/m(2) (week 1-7), daily cyclophosphamide 30 mg/m(2) (days 1-21), and twice weekly methotrexate 10 mg/m(2); (days 21-42), and daily celecoxib 100 mg to 400 mg twice daily (days1-56) followed by a 2-weeks chemotherapy break. Adverse events were determined through laboratory analysis and investigator observations. RESULTS: One objective response was observed in a patient with Hodgkin lymphoma, and 4 patients experienced disease stabilization and continued their treatment for 3 cycles (24 weeks) or more. At last follow-up, 7 patients (43%) are alive including 1 still undergoing treatment. During the overall 36 cycles of treatments received by patients, 4 grade IV toxicities and 24 grade III toxicities were observed in 11 cycles in only 10 different patients. CONCLUSION: The metronomic regimen we report here was well tolerated and associated with disease stabilization. This regimen is currently being evaluated in a national multicenter phase II study. Impact Journals LLC 2011-12-05 /pmc/articles/PMC3282100/ /pubmed/22156656 Text en Copyright: © 2011 André et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Brief Reports
André, Nicolas
Abed, Sylvie
Orbach, Daniel
Alla, Corinne Armari
Padovani, Laetitia
Pasquier, Eddy
Gentet, Jean Claude
Verschuur, Arnauld
Pilot study of a pediatric metronomic 4-drug regimen
title Pilot study of a pediatric metronomic 4-drug regimen
title_full Pilot study of a pediatric metronomic 4-drug regimen
title_fullStr Pilot study of a pediatric metronomic 4-drug regimen
title_full_unstemmed Pilot study of a pediatric metronomic 4-drug regimen
title_short Pilot study of a pediatric metronomic 4-drug regimen
title_sort pilot study of a pediatric metronomic 4-drug regimen
topic Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282100/
https://www.ncbi.nlm.nih.gov/pubmed/22156656
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