Primary chemotherapy and delayed surgery for nonmetastatic osteosarcoma of the extremities. Results in 164 patients preoperatively treated with high doses of methotrexate followed by cisplatin and doxorubicin.

Abstract

BACKGROUND:

Neoadjuvant chemotherapy is the most accepted treatment for localized osteosarcoma. This has led to a great improvement in limb-sparing surgery and in disease-free survival. Patients with a good response to preoperative chemotherapy showed a higher disease-free survival rate. Current studies examine the possibility of patients whose limbs could be rescued with a poor necrosis and a reduction of the side effects related to aggressive treatments.

METHODS:

Between September 1986 and December 1989, 164 patients entered the second neoadjuvant study conducted at the Rizzoli Institute, Bologna, Italy, for non-metastatic osteosarcoma of the extremities. Preoperative chemotherapy consisted of two cycles of high-dose methotrexate intravenously (i.v.) followed by cisplatin intraarterially and doxorubicin i.v. After surgery, patients classified as good responders (> 90% tumor necrosis) received three more cycles of these drugs, whereas poor responders (< 90% tumor necrosis) had more chemotherapy, which included ifosfamide and etoposide in addition to the other three drugs.

RESULTS:

Limb salvage was performed in 83% of cases. At an average follow-up of 54 months (36-76), 109 patients (66%) were continuously disease-free, 2 died from doxorubicin cardiotoxicity, and 52 experienced metastases and 3 had local recurrence. In two of these three patients, metastases followed local recurrence. The 5-year actuarial continuously disease-free survival rate was 63%, with no differences between good and poor responders. Excluding 20 patients who had major protocol violations, the projected continuous disease-free survival rate was 71%.

CONCLUSIONS:

With an aggressive neoadjuvant chemotherapy, it is possible to cure more than 60% of nonmetastatic osteosarcoma of the extremities, avoiding amputation in most cases. Ifosfamide and etoposide seem to be effective in patients who did not respond to preoperative chemotherapy.

• Authors: G Bacci, P Picci, S Ferrari, P Ruggieri, R Casadei, A Tienghi, A Brach del Prever, F Gherlinzoni, M Mercuri, C Monti
• Journal: Cancer (Cancer) Vol. 72 Issue 11 Pg. 3227-38 (Dec 01 1993) ISSN: 0008-543X [Print] United States
• PMID: 8242546 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Doxorubicin
• Cisplatin
• Methotrexate

Topics

• Adolescent
• Adult
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Bone Neoplasms (drug therapy, pathology, surgery)
• Cisplatin (administration & dosage, adverse effects)
• Combined Modality Therapy
• Doxorubicin (administration & dosage, adverse effects)
• Extremities (pathology, surgery)
• Female
• Femur (pathology, surgery)
• Humans
• Humerus (pathology, surgery)
• Infusions, Intravenous
• Injections, Intra-Arterial
• Male
• Methotrexate (administration & dosage, adverse effects)
• Neoplasm Recurrence, Local
• Osteosarcoma (drug therapy, pathology, secondary, surgery)
• Postoperative Complications
• Preoperative Care
• Remission Induction
• Survival Rate
• Tibia (pathology, surgery)