title: Vincristine, doxorubicin, cyclophosfamide, actinomycin D, ifosfamide, and etoposide in adult and pediatric patients with nonmetastatic Ewing sarcoma. Final results of a monoinstitutional study.
abstract: OBJECTIVE
  To investigate a six-drug combination in patients with nonmetastatic Ewing sarcoma, focusing on chemotherapy-induced necrosis and chemotherapy toxicity in adult and pediatric patients.
  
  
  METHODS
  Alternating cycles of vincristine (1.5 mg/m2), doxorubicin (80 mg/m2) and cyclophosfamide (1200 mg/m2) (weeks 0, 6, 13, 22 and 31), ifosfamide (9 g/m2), vincristine (1.5 mg/m2), and actinomycin D (1.5 mg/m2) (weeks 3, 16, 25 and 34), and ifosfamide (9 g/m2) and etoposide (450 mg/m2) (weeks 9, 19, 28 and 37) were administered. Primary chemotherapy-induced necrosis was graded: G3 (complete necrosis), G2 (microfoci of tumor cells) and G1 (macrofoci of tumor cells).
  
  
  RESULTS
  From 1996 to 1999, 50 patients with Ewing sarcoma were enrolled. The median age was 23.5 years (range, 4-56). Chemotherapy-induced necrosis (in 28 patients) was G3 in 36%, G2 in 21% and G1 in 43%. At a median follow-up of 110 months (range, 36-129), 5-year overall survival and event-free survival were 72% and 66%, respectively. According to histologic response, 5-year event-free survival was 90% in G3, 83% in G2, and 42% in G1 (P = 0.02). In adult and pediatric (<18 years) patients, the incidence of G4 leukopenia was 62% and 74%, respectively, with febrile neutropenia in 13% and 21%, respectively. G4 thrombocytopenia occurred in 3% of cycles in adults and in 7% in pediatric patients. Platelet and red blood cell transfusions were required respectively in 1% and 11% of cycles in adults and in 6% and 24% of cycles in pediatric patients.
  
  
  CONCLUSIONS
  The six-drug combination can be administered safely in adult and pediatric populations. About 40% of patients have a poor chemotherapy-induced tumor necrosis, leading to poor probability of survival. New strategies are recommended to improve survival of poor responders to the six-drug combination.
authors.affiliation: Chemotherapy, Istituto Ortopedico Rizzoli, Bologna, Italy. stefano.ferrari@ior.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
authors.forename: Emanuela
authors.initials: E
authors.lastname: Palmerini
authors.forename: Marco
authors.initials: M
authors.lastname: Alberghini
authors.forename: Eric
authors.initials: E
authors.lastname: Staals
authors.forename: Mario
authors.initials: M
authors.lastname: Mercuri
authors.forename: Enza
authors.initials: E
authors.lastname: Barbieri
authors.forename: Alessandra
authors.initials: A
authors.lastname: Longhi
authors.forename: Laura
authors.initials: L
authors.lastname: Cantero
authors.forename: Marilena
authors.initials: M
authors.lastname: Cesari
authors.forename: Massimo
authors.initials: M
authors.lastname: Abate
authors.forename: Alba
authors.initials: A
authors.lastname: Balladelli
authors.forename: Piero
authors.initials: P
authors.lastname: Picci
authors.forename: Gaetano
authors.initials: G
authors.lastname: Bacci
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D003609:Dactinomycin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D003609:Dactinomycin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D007069:Ifosfamide