High-dose chemotherapy with stem cell rescue in the primary treatment of metastatic and pelvic osteosarcoma: final results of the ISG/SSG II study

Pediatr Blood Cancer. 2014 May;61(5):840-5. doi: 10.1002/pbc.24868. Epub 2013 Nov 20.

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.

Keywords: high-dose chemotherapy; metastasis; osteosarcoma; pelvic primary tumor; stem cell rescue.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Neoplasms / mortality
  • Bone Neoplasms / secondary
  • Bone Neoplasms / therapy*
  • Child
  • Child, Preschool
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Doxorubicin / administration & dosage
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Ifosfamide / administration & dosage
  • Male
  • Methotrexate / administration & dosage
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Osteosarcoma / mortality
  • Osteosarcoma / pathology
  • Osteosarcoma / therapy*
  • Pelvic Neoplasms / mortality
  • Pelvic Neoplasms / secondary
  • Pelvic Neoplasms / therapy*
  • Pilot Projects
  • Prognosis
  • Stem Cell Transplantation*
  • Survival Rate
  • Young Adult

Substances

  • Doxorubicin
  • Cisplatin
  • Ifosfamide
  • Methotrexate