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

Trial Information

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

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.