title: Phase 2 trial of two courses of cyclophosphamide and etoposide for relapsed high-risk osteosarcoma patients.
abstract: BACKGROUND
  A phase 2 trial was carried out to assess the antineoplastic activity of 2 courses of cyclophosphamide-etoposide in relapsed osteosarcoma patients.
  
  
  METHODS
  Twenty-six relapsed osteosarcoma patients with a median age of 18.5 years (8.3-47.1) were enrolled. Seven patients were in first relapse (27%), 11 in second relapse (42%), 7 in third relapse (27%), and 1 in fourth relapse (4%). Eighteen patients had bone metastasis at study entry (69%). Cyclophosphamide was given at 4 g/m(2) on Day 1 followed by etoposide at 200 mg/m(2) on Days 2, 3, and 4. Second cyclophosphamide and etoposide was planned at 21 days to 28 days from the previous one. The primary endpoint of the study was the clinical benefit at 4 months measured as progression-free survival.
  
  
  RESULTS
  Progression-free survival at 4 months was 42%. Five patients achieved responses (19%), 9 patients had stable disease (35%), and 12 had tumor progression (46%). Overall survival (OS) at 1 year was 50%. The only grade 4 extrahematological toxicities were fever (5%), acute bronchospasm (4%) and stomatitis (18%). Six patients (23%) underwent radical surgery after cyclophosphamide and etoposide x2.
  
  
  CONCLUSIONS
  Cyclophosphamide and etoposide x2 may arrest osteosarcoma progression in a significant number of patients (54%). Osteosarcoma progression arrest after cyclophosphamide and etoposide x2 translates in a better OS. Cyclophosphamide and etoposide x2 had good tolerability and the toxicity was time-limited and resolved in all cases.
authors.affiliation: Oncoematologia Pediatrica, Regina Margherita Children's Hospital, Torino, Italy. massimo.berger@unito.it
authors.forename: M
authors.initials: M
authors.lastname: Berger
authors.forename: Berger
authors.initials: B
authors.lastname: Massimo
authors.forename: G
authors.initials: G
authors.lastname: Grignani
authors.forename: Grignani
authors.initials: G
authors.lastname: Giovanni
authors.forename: S
authors.initials: S
authors.lastname: Ferrari
authors.forename: Ferrari
authors.initials: F
authors.lastname: Stefano
authors.forename: E
authors.initials: E
authors.lastname: Biasin
authors.forename: Biasin
authors.initials: B
authors.lastname: Eleonora
authors.forename: A
authors.initials: A
authors.lastname: Brach del Prever
authors.forename: Brach Del Prever
authors.initials: Bdel P
authors.lastname: Adalberto
authors.forename: S
authors.initials: S
authors.lastname: Aliberti
authors.forename: Aliberti
authors.initials: A
authors.lastname: Sandra
authors.forename: F
authors.initials: F
authors.lastname: Saglio
authors.forename: Saglio
authors.initials: S
authors.lastname: Francesco
authors.forename: M
authors.initials: M
authors.lastname: Aglietta
authors.forename: Aglietta
authors.initials: A
authors.lastname: Massimo
authors.forename: F
authors.initials: F
authors.lastname: Fagioli
authors.forename: Fagioli
authors.initials: F
authors.lastname: Franca
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy*; D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage*; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D012516:Osteosarcoma / Q000188:drug therapy*
chemical_list: D005047:Etoposide; D003520:Cyclophosphamide