Long-term outcome for patients with nonmetastatic osteosarcoma of the extremity treated at the istituto ortopedico rizzoli according to the istituto ortopedico rizzoli/osteosarcoma-2 protocol: an updated report

J Clin Oncol. 2000 Dec 15;18(24):4016-27. doi: 10.1200/JCO.2000.18.24.4016.


Purpose: To provide an estimate of long-term prognosis for patients with osteosarcoma of the extremity treated in a single institution with neoadjuvant chemotherapy and observed for at least 10 years.

Patients and methods: Patients with nonmetastatic osteosarcoma of the extremity were preoperatively treated with high-dose methotrexate, cisplatin, and doxorubicin (ADM). Postoperatively, good responders (90% or more tumor necrosis) received the same three drugs used before surgery, whereas poor responders (less than 90% tumor necrosis) received ifosfamide and etoposide in addition to those three drugs.

Results: For the 164 patients who entered the study between September 1986 and December 1989, surgery was a limb salvage in 136 cases (82%) and a good histologic response was observed in 117 patients (71%). At a follow-up ranging from 10 to 13 years (median, 11.5 years), 101 patients (61%) remained continuously free of disease, 61 relapsed, and two died of ADM-induced cardiotoxicity. There were no differences in prognosis between good and poor responding patients. ADM-induced cardiotoxicity (six patients), male infertility (10 of the 12 assessable patients), and second malignancies (seven patients) were the major complications of chemotherapy. Despite the large number of limb salvages performed, only four local recurrences (2.4%) were registered.

Conclusion: With an aggressive neoadjuvant chemotherapy, it is possible to cure more than 60% of patients with nonmetastatic osteosarcoma of the extremity and amputation may be avoided in more than 80% of them. Because local or systemic relapses, myocardiopathies, and second malignancies are possible even 5 years or more after the beginning of treatment, a long-term follow-up is recommended for these patients.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / surgery*
  • Child
  • Cisplatin / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Etoposide / administration & dosage
  • Extremities
  • Female
  • Fertility / drug effects
  • Follow-Up Studies
  • Humans
  • Ifosfamide / administration & dosage
  • Male
  • Methotrexate / administration & dosage
  • Neoadjuvant Therapy
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / surgery
  • Neoplasms, Second Primary / drug therapy
  • Neoplasms, Second Primary / etiology
  • Neoplasms, Second Primary / surgery
  • Osteosarcoma / diagnostic imaging
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / surgery*
  • Patient Compliance
  • Postoperative Complications / etiology
  • Postoperative Complications / surgery
  • Radiography
  • Reconstructive Surgical Procedures
  • Reoperation
  • Survival Rate


  • Etoposide
  • Doxorubicin
  • Cisplatin
  • Ifosfamide
  • Methotrexate