Methotrexate, Trimetrexate Glucuronate, and Leucovorin in Treating Patients With Refractory or Recurrent Osteosarcoma

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant osteosarcoma
• High-grade disease
• Recurrent or refractory disease after prior standard chemotherapy comprising methotrexate, doxorubicin, cisplatin, and ifosfamide
• No low-grade osteosarcoma
• No parosteal or periosteal sarcoma
• No osteosarcoma arising in premalignant bony lesions (e.g., Paget's disease) OR in a prior radiotherapy field
• No symptomatic or known brain or leptomeningeal involvement

PATIENT CHARACTERISTICS:

Age

• 1 to 35

Performance status

• Karnofsky 70-100% (for patients > 16 years of age)
• Lansky 70-100% (for patients ≤ 16 years of age)

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm^3
• Platelet count ≥ 75,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 times normal
• AST and ALT ≤ 5 times normal
• Albumin ≥ 2 g/dL
• No clinically significant liver disease

Renal

• Creatinine ≤ 1.5 times normal OR
• Creatinine clearance or radioisotope glomerular filtration rate ≥ lower limit of normal

Cardiovascular

• Shortening fraction ≥ 27% by echocardiogram OR
• Ejection fraction ≥ 50% by gated radionuclide study
• No congestive heart failure
• No angina pectoris
• No myocardial infarction within the past year
• No uncontrolled arterial hypertension
• No uncontrolled arrhythmias

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of significant neurological or psychiatric disorder
• No active infection
• No symptomatic peripheral neuropathy ≥ grade 2
• No other serious illness or medical condition

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 7 days since prior biologic therapy
• At least 6 months since prior allogeneic stem cell transplantation AND no evidence of active graft-versus-host disease
• No concurrent sargramostim (GM-CSF)

Chemotherapy

• See Disease Characteristics
• More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas)

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 2 weeks since prior local palliative radiotherapy (small port)
• At least 6 months since prior craniospinal radiotherapy
• At least 6 months since prior radiotherapy to ≥ 50% of the pelvis
• At least 6 weeks since prior substantial radiotherapy to the bone marrow

Surgery

• Not specified

Other

• Recovered from prior therapy
• More than 30 days since prior and no other concurrent investigational drugs
• More than 30 days since prior and no concurrent participation in another clinical trial
• No concurrent medications that may interact with study drugs