title: Pilot study of a pediatric metronomic 4-drug regimen.
abstract: 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 paediatric patients with refractory or relapsing various tumour types.
  
  
  METHODS
  From November 2008 to December 2010, in three academic paediatric 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/m2 (week 1-7), daily cyclophosphamide 30 mg/m2 (days 1-21), and twice weekly methotrexate 10 mg/m² (days 21-42), and daily celecoxib 100 mg to 400 mg twice daily (days 1-56) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Service d'Hématologie et Oncologie Pédiatrique, Hôpital pour Enfants de La Timone, Marseille, France. Nicolas.andre@ap-hm.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: André
authors.forename: Sylvie
authors.initials: S
authors.lastname: Abed
authors.forename: Daniel
authors.initials: D
authors.lastname: Orbach
authors.forename: Corinne Armari
authors.initials: CA
authors.lastname: Alla
authors.forename: Laetitia
authors.initials: L
authors.lastname: Padovani
authors.forename: Eddy
authors.initials: E
authors.lastname: Pasquier
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Gentet
authors.forename: Arnauld
authors.initials: A
authors.lastname: Verschuur
mesh_terms: D059250:Administration, Metronomic; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000068579:Celecoxib; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy*; D010865:Pilot Projects; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D011720:Pyrazoles; D013449:Sulfonamides; D014747:Vinblastine; D003520:Cyclophosphamide; D000068579:Celecoxib; D008727:Methotrexate