title: Oral etoposide in relapsed or refractory Ewing sarcoma: a monoinstitutional experience in children and adolescents.
abstract: OBJECTIVE
  To assess the efficacy and toxicity of low-dose oral etoposide (VP) 16 in relapsing/refractory Ewing sarcoma.
  
  
  METHODS
  The records of all patients treated at our department between 1989 and 2012 for relapsing/refractory Ewing sarcoma who received oral VP-16 were analyzed. The dose was 40 mg/m2 daily for 21 consecutive days in every 28. Response was assessed after 2/3 cycles according to Response Evaluation Criteria in Solid Tumors 1.0.
  
  
  RESULTS
  A total of 46 of 58 patients completed at least 2 cycles; 12 suspended the treatment earlier due to rapid disease progression. The patients' median age at diagnosis was 14 years and 25/58 had metastatic disease. All patients received intensive polychemotherapy including VP-16 IV as first- (n = 53) or second-line (n = 5) treatment; 21/58 had myeloablative regimens with peripheral blood stem cell rescue, and 1 underwent allogeneic stem cell transplantation. Oral VP-16 was prescribed as 2nd-, 3rd-, and 4th-line treatment for 19, 27, and 12 patients, respectively. The cycles administered totaled 241 (median 3, mean 4 per patient; range 1-14). A total of 46 of 58 patients were evaluable: 11 responded (9 partial remission, 1 very good partial remission, 1 complete remission) and 10 were stable, the response lasting a mean of 8 months. Hematologic toxicity G3/G4 (in 164/241 evaluable cycles) occurred in 15%, 16%, and 11% of cycles for leukocytes, hemoglobin, and platelets, respectively. There were 5 cases of pneumonia. Two patients developed secondary leukemia after receiving 12 and 14 cycles.
  
  
  CONCLUSIONS
  Low-dose oral VP-16 may be suitable in a palliative setting with an acceptable toxicity. The risk of secondary leukemia is in line with reports in the literature.
authors.affiliation: Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Marta G
authors.initials: MG
authors.lastname: Podda
authors.affiliation: Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Luksch
authors.affiliation: Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Puma
authors.affiliation: Pediatric Radiotherapy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Gandola
authors.affiliation: Radiology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Morosi
authors.affiliation: Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Terenziani
authors.affiliation: Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrari
authors.affiliation: Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Casanova
authors.affiliation: Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Spreafico
authors.affiliation: Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Meazza
authors.affiliation: Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Catania
authors.affiliation: Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Schiavello
authors.affiliation: Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Biassoni
authors.affiliation: Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Chiaravalli
authors.affiliation: Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Massimino
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy*; D002648:Child; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced*; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D012008:Recurrence; D012189:Retrospective Studies; D012512:Sarcoma, Ewing / Q000188:drug therapy*; D059005:Topoisomerase II Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D059005:Topoisomerase II Inhibitors; D005047:Etoposide