title: Phase II study of cisplatin and oral VP16 in patients with refractory or relapsed Ewing sarcoma.
abstract: BACKGROUND
  Phase II trials demonstrate the activity of cisplatin in patients with refractory Ewing sarcoma family tumours (ESFT) and also the feasibility of giving cisplatin with oral VP16 in a variety of different cancers. This trial was conducted to evaluate the activity and toxicity profile of this combination delivered as outpatient therapy in patients with refractory/relapsed ESFT.
  
  
  METHODS
  Cisplatin was administered on days 1, 8 and 15 and days 29, 36 and 43 (70 mg/m(2)/dose for patients <21 years of age and 50 mg/m(2)/dose ≥21 years). VP16 was administered at a dose of 50 mg/m(2) on days 1-15 and days 29-43 inclusive. A three-stage Fleming statistical design was used for analysis.
  
  
  RESULTS
  Between January 2003 and October 2006, 45 patients aged between 5 and 46 years (median 19) were enrolled. Thirty-eight were evaluable for response. Patients had previously received one to three lines of chemotherapy (median = one). Seventy-three per cent of the patients had grade 3/4 neutropenia, 20 % developed fever, 40 % had grade 3/4 anaemia, 68 % grade 3/4 thrombocytopenia and 16 % grade 2/3 ototoxicity. Measured response after 2 cycles: 0 CR, 7 PR (18 %), 13 SD (34 %), 18 PD (48 %). There was excellent concordance between unidimensional and bidimensional criteria in 31 of 33 responses (94 %). PFS at 1 year was 39 %, with a median PFS of 6 months. Overall survival at 1 year was 44 %; median survival was 11 months.
  
  
  CONCLUSIONS
  Cisplatin combined with oral VP16 is well tolerated and has acceptable side effects, but limited clinical activity in refractory/relapsed ESFT.
authors.affiliation: Department of Paediatric Oncology, Institut Gustave Roussy, Villejuif, France. cormacowens@yahoo.com
authors.forename: Cormac
authors.initials: C
authors.lastname: Owens
authors.forename: Valerie
authors.initials: V
authors.lastname: Laurence
authors.forename: Lofti
authors.initials: L
authors.lastname: Benboubker
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Defachelles
authors.forename: Didier
authors.initials: D
authors.lastname: Cupissol
authors.forename: Hervé
authors.initials: H
authors.lastname: Rubie
authors.forename: Hervé
authors.initials: H
authors.lastname: Brisse
authors.forename: Annie
authors.initials: A
authors.lastname: Rey
authors.forename: Liliane
authors.initials: L
authors.lastname: Ollivier
authors.forename: Dominique
authors.initials: D
authors.lastname: Couanet
authors.forename: Christiane
authors.initials: C
authors.lastname: Baunin
authors.forename: Céline Mahier
authors.initials: CM
authors.lastname: Aït-Oukhatar
authors.forename: Odile
authors.initials: O
authors.lastname: Oberlin
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000401:mortality
chemical_list: D005047:Etoposide; D002945:Cisplatin