• Rate of in vivo histologic response [ Designated as safety issue: No ]
  
• Event-free survival [ Designated as safety issue: No ]
  
• Overall survival [ Designated as safety issue: No ]
  

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

Patients are followed within 4 weeks, every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 100 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed newly diagnosed osteosarcoma

  • No more than 1 month since prior diagnostic biopsy
  • Nonmetastatic malignant high-grade osteosarcoma of bone
  • Histologically confirmed metastatic disease allowed
  • Unresectable primary disease allowed
• No low-grade, parosteal, or periosteal osteosarcoma

PATIENT CHARACTERISTICS:

Age:

• 25 and under

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 8.0 g/dL

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• ALT less than 5 times normal

Renal:

• Creatinine no greater than 1.5 times normal
• Creatinine clearance or radioisotope glomerular filtration rate greater than 70 mL/min

Cardiovascular:

• Shortening fraction at least 27% by echocardiogram or MUGA
• Ejection fraction at least 45% by echocardiogram or MUGA

Other:

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics

Surgery:

• Not specified

Other:

• No other concurrent therapy with no evidence of progressive disease