title: Metronomic etoposide/cyclophosphamide/celecoxib regimen given to children and adolescents with refractory cancer: a preliminary monocentric study.
abstract: BACKGROUND
  Metronomic chemotherapy (MC) is the administration of chemotherapy at doses below the maximal tolerated dose on a frequent schedule of administration, with no prolonged drug-free breaks.
  
  
  OBJECTIVE
  The aim of this research was to assess the effectiveness and tolerance of a metronomic etoposide/ cyclophosphamide/celecoxib regimen in children and adolescents with refractory cancer.
  
  
  METHODS
  This retrospective, single-center study evaluated the use of MC with etoposide 25 mg/m(2).d(-1) (days 1-14), cyclophosphamide 25 mg/m(2) d(-1) (days 15-28), and celecoxib 100 to 400 mg/d (days 1-28), in children with refractory, or high-risk relapsing, cancer. Adverse events were determined through laboratory analyses and investigator observations.
  
  
  RESULTS
  From January 2005 to December 2007, 17 children and adolescents were treated. The best responses observed were stabilizations of the disease that lasted over 20 weeks in 7 patients (41%). Most importantly, in 4 patients (24%) antalgic treatment could be transiently diminished or stopped, and in 1 patient (6%) oxygen support could be stopped for several weeks. Four grade IV platelet toxicities were noted in 3 patients; 2 grade IV anemia occurred in 2 patients (who had platelet and red blood cell transfusions before initiation of treatment); and 1 patient had grade III neutropenia. No other grade III or IV toxicities were noted. Grade II alopecia and stomatitis were observed in 1 patient and grade II vomiting was observed in 2 patients. One patient with meningeal carcinomatosis developed bilateral subdural hematoma for which the role of MC could not be ruled out. Circulating endothelial cells were elevated in 3 out of 3 patients in whom they were quantified and who were progressing while under MC.
  
  
  CONCLUSIONS
  The MC regimen we report here was associated with disease stabilization without major toxicities. This assessment of MC in children and adolescents warrants further studies.
authors.affiliation: Service d'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: Angelique
authors.initials: A
authors.lastname: Rome
authors.forename: Carole
authors.initials: C
authors.lastname: Coze
authors.forename: Laetitia
authors.initials: L
authors.lastname: Padovani
authors.forename: Eddy
authors.initials: E
authors.lastname: Pasquier
authors.forename: Laurence
authors.initials: L
authors.lastname: Camoin
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Gentet
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068579:Celecoxib; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D011720:Pyrazoles / Q000008:administration & dosage; D012189:Retrospective Studies; D013449:Sulfonamides / Q000008:administration & dosage
chemical_list: D011720:Pyrazoles; D013449:Sulfonamides; D005047:Etoposide; D003520:Cyclophosphamide; D000068579:Celecoxib