| Inclusion Criteria: | 1) Patients with recurrent high grade osteosarcoma, Ewing's sarcoma, unresectable or locally recurrent unresectable chondrosarcoma. Histologic diagnosis from initial diagnosis is acceptable for local recurrences, however, biopsy confirmation is strongly recommended. For isolated pulmonary recurrences, biopsy is required. Histologic diagnosis will be determined at the treating institution, central review is not required. For patients with chondrosarcoma, determination of "unresectable" will be made by the treating oncologist and surgeon at the treating institution.
2) Age greater than or equal to 4 years.
3) Measurable disease: defined as lesions that can be measured in at least one dimension by medical imaging techniques. Ascites, pleural effusions, and bone marrow disease will not be considered measurable disease.
4) Performance status: Patients greater than or equal to 18 years must have an ECOG performance of less than or equal to 2. Patients less than 18 years and older than 10 years must have a Karnofsky score of greater than or equal to 50%. Patients less than 10 years must have a Lansky score of greater than or equal to 50.
5) Osteosarcoma and Ewing's sarcoma: patients must have progressed after standard therapy, and may have received no more than 2 additional salvage regimens. Chondrosarcoma: must be unresectable or locally recurrent and unable to be completely resected.
6) Patients must have recovered (defined as toxicity < grade 2) from toxic effects of all prior therapy before entering onto study.
7) A treatment free interval of at least 2 weeks since the last dose of myelosuppressive therapy is required.
8) At least a 6 month interval since last dose of myeloablative therapy or total body irradiation is required.
9) A minimum of 6 weeks since local radiation and 4 months from extensive radiation (greater than 50% of pelvis or cranial spinal radiation) is required.
10) Patients who received filgrastim on a previous cycle of chemotherapy must be off filgrastim for at least 72 hours prior to entry onto study.
11) Adequate bone marrow function with an ANC greater than or equal to 1500/mm3, platelet count greater than or equal to 100,000/mm3 (transfusion independent) and hemoglobin greater than 8.0 g/dl (transfusions permitted).
12) Adequate renal function with normal age adjusted serum creatinine or creatinine clearance or radioisotope GFR greater > 70 ml/min/1.73m2. For patients over 15 years of age, maximum serum creatinine must be less than or equal to 1.5. For patients between 10 and 15 years of age, maximum serum creatinine must be less than or equal to 1.2. For patients between 5 and 10 years of age, maximum serum creatinine must be less than or equal to 1.0. For patients less than 5, maximum serum creatinine must be less than or equal to 0.8.
13) Patients must have adequate liver function, defined as bilirubin within normal limits, SGPT(ALT) less than or equal to 2.5 x ULN. For patients with documented Gilbert syndrome, total bilirubin greater than ULN may be acceptable if the PI in consultation with Medical Affairs, Aventis Oncology (908-243-6459) approves a special exemption for treatment on this protocol.
14) Neuropathy (sensory or motor) due to prior chemotherapy, if present, must be less than or equal to grade 1. Neuropathy (sensory or motor) due to prior surgery or tumor involvement must be less than or equal to grade 2 and stable or improving.
15) Subjects of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which may include abstinence, while being treated on this study and for 3 months afterward.
16) Informed consent: All patients or their legal guardians (if the patient is less than 18 years of age) must sign a document of informed consent indicating their awareness of the investigational nature and the risks of the study. When appropriate the patient will be included in all discussions in order to obtain assent. |