RATIONALE: Drugs used in chemotherapy, such as cisplatin, doxorubicin, and methotrexate,
work in different ways to stop tumor cells from dividing so they stop growing or die.
Combining pamidronate with chemotherapy may prevent bone metastases and reduce the chance of
bone replacement problems by strengthening bones in patients who are undergoing surgery for
PURPOSE: Phase II trial to study the effectiveness of combining neoadjuvant and adjuvant
pamidronate with induction and maintenance chemotherapy in treating patients who have newly
- Determine the safety and feasibility of pamidronate with standard induction and
maintenance chemotherapy in patients with newly diagnosed high-grade osteosarcoma.
- Determine the frequency of favorable tumor necrosis produced in patients treated with
- Determine the event-free survival of patients without metastatic disease at
presentation treated with this regimen.
- Determine the prosthesis failure-free survival of patients treated with this regimen
and who ultimately undergo limb preservation surgery with insertion of an
OUTLINE: Patients are stratified according to extent of disease (localized vs metastatic).
- Induction therapy: Patients receive standard chemotherapy comprising cisplatin IV over
4 hours and doxorubicin IV over 15-30 minutes on weeks 0 and 5 and high-dose
methotrexate IV over 4 hours on weeks 3, 4, 8, and 9. Patients also receive pamidronate
IV over 2-4 hours beginning approximately 3 days after initiation of chemotherapy on
week 0 and repeating once every 4 weeks. Treatment continues in the absence of disease
progression or unacceptable toxicity.
- Surgery*: Patients undergo surgical resection of primary tumor on week 10 and then
proceed to maintenance therapy. Patients with metastatic disease undergo further
surgery of metastatic sites after recovery from definitive resection of the primary
tumor before proceeding to maintenance therapy.
NOTE: *Patients who have undergone definitive surgical resection before study entry may
proceed to maintenance therapy or, if appropriate, surgical resection of metastatic disease
- Maintenance therapy: Patients receive standard chemotherapy comprising cisplatin IV
over 4 hours on weeks 0 and 5; doxorubicin IV over 15-30 minutes on weeks 0, 5, 10, and
15; and high-dose methotrexate IV over 4 hours on weeks 3, 4, 8, 9, 13, 14, 18, and 19.
Patients also receive pamidronate as in induction therapy for up to 1 year. Treatment
continues in the absence of disease progression or unacceptable toxicity.
Patients are followed monthly for 1 year.
PROJECTED ACCRUAL: A total of 75 patients (50 with localized disease; 25 with metastatic
disease) will be accrued for this study within 3-4 years.
- Histologically confirmed high-grade osteosarcoma
- Newly diagnosed
- Previously untreated
- Prior definitive surgical resection of primary tumor allowed
- No history of Paget's disease
- Any age
- ECOG 0-2
- Not specified
- Platelet count at least 100,000/mm^3
- Absolute neutrophil at least 1,000/mm^3
- AST no greater than 3 times upper limit of normal (ULN)
- Bilirubin no greater than 1.5 times ULN
- Creatinine no greater than 1.5 times ULN
- Shortening fraction at least 28% by echocardiogram OR
- Ejection fraction at least 50% by radionuclide angiogram
- No history of pericarditis or myocarditis
- No history of symptomatic arrhythmia
- No history of symptomatic cardiac conduction abnormalities
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No history of other cancer
PRIOR CONCURRENT THERAPY:
- Not specified
- No prior chemotherapy
- Not specified
- No prior radiotherapy
- See Disease Characteristics
- No prior treatment for cancer
- No concurrent enrollment on another therapeutic study