title: Metronomic chemotherapy with the COMBAT regimen in advanced pediatric malignancies: a multicenter experience.
abstract: BACKGROUND
  The outcome of children with refractory/relapsed malignancies remains poor and novel therapies are urgently required. One of the promising approaches is metronomic chemotherapy. We present the clinical results of 74 children with advanced solid tumors treated according to treatment recommendation with data registry in three European pediatric centers.
  
  
  METHODS
  COMBAT (Combined Oral Metronomic Biodifferentiating Antiangiogenic Treatment) included low-dose daily temozolomide, etoposide, celecoxib, vitamin D, fenofibrate and retinoic acid. From 2004 to 2010, 74 children were enrolled.
  
  
  RESULTS
  The 2-year overall survival (OS) was 43.1% (median 15.4, range 1.3-69.9 months). Of the 74 patients, 50 patients (68%) died and 24 are alive: 6 (8%) with progressive disease, 7 (9%) with stable disease/partial response and 11 (15%) in complete response. Median time to response was 6 months. Of 62 patients with initially measurable disease, 25 (40%) had radiological response or stable disease. Fourteen of 25 showing clinical benefit responded within the first 6 months. The treatment was well tolerated on an outpatient basis. Regarding non-hematological toxicity of grade ≥2, hepatotoxicity of grade 3 occurred in 8 children and grade 3 cheilitis in 16 children.
  
  
  CONCLUSIONS
  COMBAT is a feasible and effective treatment option for patients with relapsing/refractory malignancies. The treatment is well tolerated with a low acute toxicity profile.
authors.affiliation: Department of Pediatric Oncology, University Hospital Brno, School of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: D
authors.initials: D
authors.lastname: Zapletalova
authors.forename: N
authors.initials: N
authors.lastname: André
authors.forename: L
authors.initials: L
authors.lastname: Deak
authors.forename: M
authors.initials: M
authors.lastname: Kyr
authors.forename: V
authors.initials: V
authors.lastname: Bajciova
authors.forename: P
authors.initials: P
authors.lastname: Mudry
authors.forename: L
authors.initials: L
authors.lastname: Dubska
authors.forename: R
authors.initials: R
authors.lastname: Demlova
authors.forename: Z
authors.initials: Z
authors.lastname: Pavelka
authors.forename: K
authors.initials: K
authors.lastname: Zitterbart
authors.forename: J
authors.initials: J
authors.lastname: Skotakova
authors.forename: K
authors.initials: K
authors.lastname: Husek
authors.forename: A
authors.initials: A
authors.lastname: Martincekova
authors.forename: P
authors.initials: P
authors.lastname: Mazanek
authors.forename: T
authors.initials: T
authors.lastname: Kepak
authors.forename: M
authors.initials: M
authors.lastname: Doubek
authors.forename: L
authors.initials: L
authors.lastname: Kutnikova
authors.forename: D
authors.initials: D
authors.lastname: Valik
authors.forename: J
authors.initials: J
authors.lastname: Sterba
mesh_terms: D059250:Administration, Metronomic; D000293:Adolescent; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068579:Celecoxib; D002648:Child; D002675:Child, Preschool; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005047:Etoposide / Q000008:administration & dosage; D005060:Europe; D005240:Feasibility Studies; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage; D006801:Humans; D007223:Infant; D015474:Isotretinoin / Q000008:administration & dosage; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D011720:Pyrazoles / Q000008:administration & dosage; D012042:Registries; D013449:Sulfonamides / Q000008:administration & dosage; D000077204:Temozolomide; D014807:Vitamin D / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D014807:Vitamin D; D005047:Etoposide; D003606:Dacarbazine; D015474:Isotretinoin; D000068579:Celecoxib; D011345:Fenofibrate; D000077204:Temozolomide