Current Clinical Trials

Most recurrences of osteosarcoma develop within 2 to 3 years after treatment completion. Late recurrences are rare, occurring in 0.6% to 3.7% of patients.[1-3] Recurrence of osteosarcoma is most often in the lung. Patients with recurrent osteosarcoma should be assessed for surgical resectability, as they may sometimes be cured with aggressive surgical resection with or without chemotherapy.[4-9] The ability to achieve a complete resection of recurrent disease is the most important prognostic factor at first relapse, with a 5-year survival rate of 20% to 45% following complete resection of metastatic pulmonary tumors and a 20% survival rate following complete resection of metastases at other sites.[8-11] Repeated resections of pulmonary recurrences can lead to extended disease control and possibly cure for some patients.[11,12] Survival for patients with unresectable metastatic disease is less than 5%.[8,13] Factors that suggest a better outcome include fewer pulmonary nodules, unilateral pulmonary metastases,[14] or longer intervals between primary tumor resection and metastases.[8,10,15] Resection of metastatic disease followed by observation alone results in low overall survival and disease-free survival. Patients with osteosarcoma who develop bone metastases have a poor prognosis. In one large series, the 5-year event-free survival (EFS) rate was 11%.[16] Patients with late solitary bone relapse have a 5-year EFS rate of approximately 30%.[16-18] A high percentage of patients with pulmonary nodules identified in only one lung who underwent staged bilateral thoracotomy were found to have palpable nodules in both lungs that were not visualized on a computed tomography scan. This suggests that patients with unilateral nodules may benefit from bilateral exploration.[14] The postrelapse outcome of patients who have a local recurrence is worse than that for patients who relapse with metastases alone.[19-21]

Two retrospective, single-institution series reported 10% to 40% survival following local recurrence without associated systemic metastasis.[22-25] The survival for patients with local recurrence and either prior or concurrent systemic metastases is poor.[24] The incidence of local relapse was higher in patients who had a poor pathologic response to chemotherapy in the primary tumor and in patients with inadequate surgical margins.[19,23]

The role of systemic chemotherapy is not well defined. The selection of further systemic treatment depends on many factors, including the site of recurrence, the patient’s previous primary treatment, and individual patient considerations. Ifosfamide alone with mesna uroprotection, or in combination with etoposide, has shown activity in as many as one-third of patients with recurrent osteosarcoma who have not previously received this drug.[26-29] Cyclophosphamide and etoposide have activity in recurrent osteosarcoma.[30] Peripheral blood stem cell transplant utilizing high-dose chemotherapy does not appear to improve outcome. High-dose samarium-153-EDTMP coupled with peripheral blood stem cell support may provide significant pain palliation in patients with bone metastases.[31-34] Clinical trials (phases I and II) are appropriate for patients with unresectable metastatic disease and should be considered.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent osteosarcoma and recurrent childhood malignant fibrous histiocytoma of bone. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

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