The Cancer Center at the University of Virginia Health System invites patients who are younger than 21 years old and diagnosed with osteosarcoma to participate in a research study.

The purpose of this study is to determine how best to treat patients with osteosarcoma by comparing how patients do when treated with different anti-cancer drugs.

Participants will begin treatment with the standard drugs for osteosarcoma therapy: doxorubicin, cisplatin, and methotrexate (MAP). Following 10 weeks of therapy, subjects will have surgery to take out the tumor(s).If 90% or more of the tumor cells have been killed, this will be called a good tumor response. If less than 90% of the tumor cells have been killed, this will be called a poor tumor response. If you have a good response to MAP, you will be receive one of the following two courses of treatment: either you will continue to receive MAP for approximately 7 months, or you may receive MAPifn, which is methotrexate, adriamycin, cisplatin, and Pegylated interferon alfa-2b for 7 months, and then up to 2 years of Pegylated interferon alfa-2b, as long as the treatment does not cause significant side effects and there is no evidence that your cancer has progressed. If you have a poor response to MAP, you will receive one of the following courses of treatment: MAP for approximately 7 months, or MAPIE (methotrexate, adriamycin, cisplatin and ifosfamide, etoposide) for approximately 10 months as long as your side effects are not too bad and your cancer has not progressed.

If you take part in this study, you will have the following tests and procedures: surgery, biopsy, physical examinations, blood tests, urine tests, pregnancy tests, scans (such as an MRI, xray, CT scan, and bone scan), echocardiograms, hearing tests, and nuclear medicine scans. You will receive physical exams and blood tests for a few years after treatment is done so study doctors can watch you for any effects of the treatment. We will ask you to fill out questionnaires regarding how you are doing.

The participant's insurance company will be billed for the costs of the medications, procedures, and tests. There will be no financial compensation for participating in this study.