title: High-dose chemotherapy with stem cell rescue in the primary treatment of metastatic and pelvic osteosarcoma: final results of the ISG/SSG II study.
abstract: BACKGROUND
  Patients with metastatic osteosarcoma at diagnosis or axial primary tumors have a poor prognosis. The aim of the study was to evaluate the feasibility and efficacy of intensified treatment with high-dose chemotherapy (HDCT) and stem cell rescue in this group.
  
  
  METHODS
  From May 1996 to August 2004, 71 patients were included in a Scandinavian-Italian single arm phase II study. Preoperative chemotherapy included methotrexate, doxorubicin, cisplatin and ifosfamide, and postoperative treatment consisted of two cycles of doxorubicin, one cycle of cyclophosphamide and etoposide and two courses of high-dose etoposide and carboplatin with stem cell rescue.
  
  
  RESULTS
  Twenty-nine patients (43%) received two courses and 10 patients (15%) received one course of HDCT. HDCT was associated with significant toxicity, but no treatment-related deaths were recorded. Fourteen patients (20%) had disease progression before completion of the study protocol, and only 29/71 patients (41%) received the full planned treatment. Median event-free survival (EFS) was 18 months, and estimated 5-year EFS was 27%. Median overall survival (OS) was 34 months, and estimated 5-year OS was 31%. When patients who did not receive HDCT due to disease progression were excluded, there was no difference in EFS (P = 0.72) or OS (P = 0.49) between patients who did or did not receive HDCT.
  
  
  CONCLUSIONS
  The administration of high-dose chemotherapy with stem cell rescue was feasible, but associated with significant toxicity. Patient outcome seemed comparable to previous studies using conventional chemotherapy. We conclude that HDCT with carboplatin and etoposide should not be further explored as a treatment strategy in high-risk osteosarcoma.
authors.affiliation: Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Kjetil
authors.initials: K
authors.lastname: Boye
authors.forename: Adalberto Brach
authors.initials: AB
authors.lastname: Del Prever
authors.forename: Mikael
authors.initials: M
authors.lastname: Eriksson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Saeter
authors.forename: Amelia
authors.initials: A
authors.lastname: Tienghi
authors.forename: Paula
authors.initials: P
authors.lastname: Lindholm
authors.forename: Franca
authors.initials: F
authors.lastname: Fagioli
authors.forename: Sigmund
authors.initials: S
authors.lastname: Skjeldal
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
authors.forename: Kirsten Sundby
authors.initials: KS
authors.lastname: Hall
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D010386:Pelvic Neoplasms / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D010865:Pilot Projects; D011379:Prognosis; D033581:Stem Cell Transplantation; D015996:Survival Rate; D055815:Young Adult
chemical_list: D004317:Doxorubicin; D002945:Cisplatin; D007069:Ifosfamide; D008727:Methotrexate
keywords: high-dose chemotherapy; metastasis; osteosarcoma; pelvic primary tumor; stem cell rescue