Osteosarcoma: Outcome of Therapy Based on Histologic Response. A Collaborative Effort of the POB/NCI, Texas Children's Hospital and University of Oklahoma.

OBJECTIVES:

• Determine the rate of in vivo histologic response in patients with osteosarcoma treated with neoadjuvant cisplatin, methotrexate, and doxorubicin with dexrazoxane (as cardioprotection).
• Determine the event-free and overall survival of patients with nonmetastatic disease who show good response to neoadjuvant therapy and receive adjuvant therapy with the same regimen.
• Determine the event-free survival of patients with nonmetastatic disease who show poor response to neoadjuvant therapy and receive adjuvant therapy with the same regimen.
• Determine the event-free survival and overall survival of patients with metastatic disease who receive neoadjuvant therapy.

OUTLINE: This is a multicenter study.

• Neoadjuvant therapy: Patients receive neoadjuvant chemotherapy comprising dexrazoxane IV over 15 minutes, doxorubicin IV over 15 minutes, and cisplatin IV over 4 hours on days 1 and 2 in week 0. Patients also receive methotrexate IV over 4 hours followed by leucovorin calcium in weeks 3 and 4. Patients then receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning 24 hours after completion of chemotherapy and continuing until blood counts recover. Treatment repeats every 5 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
• Surgical resection: Patients undergo definitive surgery in week 11.
• Adjuvant therapy: Patients receive dexrazoxane, doxorubicin, cisplatin, methotrexate, and leucovorin calcium as in neoadjuvant therapy*. Treatment repeats every 5 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

NOTE: *Cisplatin is not administered in courses 3 and 4 of adjuvant therapy