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Metronomic Four-Drug Regimen Has Anti-tumor Activity in Pediatric Low-Grade Glioma; The Results of a Phase II Clinical Trial

Verschuur, Arnauld ; Heng-Maillard, Marie-Amélie ; Dory-Lautrec, Philippe ; Truillet, Romain ; Jouve, Elisabeth ; Chastagner, Pascal ; Leblond, Pierre ; Aerts, Isabelle ; Honoré, Stéphane ; Entz-Werle, Natasha ; Sirvent, Nicolas ; Gentet, Jean-Claude ; Corradini, Nadège ; André, Nicolas

Frontiers in pharmacology, 2018-09, Vol.9, p.00950-00950 [Periódico revisado por pares]

Switzerland: Frontiers Research Foundation

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  • Título:
    Metronomic Four-Drug Regimen Has Anti-tumor Activity in Pediatric Low-Grade Glioma; The Results of a Phase II Clinical Trial
  • Autor: Verschuur, Arnauld ; Heng-Maillard, Marie-Amélie ; Dory-Lautrec, Philippe ; Truillet, Romain ; Jouve, Elisabeth ; Chastagner, Pascal ; Leblond, Pierre ; Aerts, Isabelle ; Honoré, Stéphane ; Entz-Werle, Natasha ; Sirvent, Nicolas ; Gentet, Jean-Claude ; Corradini, Nadège ; André, Nicolas
  • Assuntos: angiogenesis ; Cancer ; Chemotherapy ; Development and progression ; drug repositioning ; Drug therapy ; Gliomas ; Human health and pathology ; immunity ; Life Sciences ; low grade glioma ; Methods ; metronomic chemotherapy ; Neurobiology ; Neurons and Cognition ; Patient outcomes ; pediatric oncology ; Pediatrics ; Pharmaceutical sciences ; Pharmacology
  • É parte de: Frontiers in pharmacology, 2018-09, Vol.9, p.00950-00950
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    Edited by: Giuseppe Giaccone, Georgetown University, United States
    Reviewed by: Min Hee Kang, Texas Tech University Health Sciences Center, United States; Yun Dai, Virginia Commonwealth University, United States
    This article was submitted to Cancer Molecular Targets and Therapeutics, a section of the journal Frontiers in Pharmacology
  • Descrição: 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 has shown its efficacy in adult tumor types such as breast and ovarian cancer and has to some extent been studied in pediatrics. To assess the anti-tumor activity and toxicity of a four-drug metronomic regimen in relapsing/refractory pediatric brain tumors (BT) with progression-free survival (PFS) after two cycles as primary endpoint. Patients ≥4 to 25 years of age were included with progressing BT. Treatment consisted of an 8-week cycle of celecoxib, vinblastine, and cyclophosphamide alternating with methotrexate. Kepner and Chang two-steps model was used with 10 patients in the first stage. If stabilization was observed in ≥2 patients, 8 additional patients were recruited. Assessment was according WHO criteria with central radiology review. Twenty-nine patients (27 evaluable) were included in two groups: ependymoma (group 1, = 8), and miscellaneous BT (group 2): 3 medulloblastoma (MB), 5 high grade glioma (HGG), 11 low grade glioma (LGG), 2 other BT. After first stage, recruitment for ependymoma was closed [one patient had stable disease (SD) for 4 months]. Cohort 2 was opened for second stage since 1 HGG and 3 LGG patients had SD after two cycles. Recruitment was limited to LGG for the second stage and 2 partial responses (PR), 6 SD and 2 progressive disease (PD) were observed after two cycles. Of these patients with LGG, median age was 10 years, nine patients received vinblastine previously. Median number of cycles was 6.8 (range: 1-12). Treatment was interrupted in five patients for grade 3/4 toxicity. This regimen is active in patients with LGG, even if patients had previously received vinblastine. Toxicity is acceptable. This study was registered under clinicaltrials.gov - NCT01285817; EUDRACT nr: 2010-021792-81.
  • Editor: Switzerland: Frontiers Research Foundation
  • Idioma: Inglês
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