|Inclusion Criteria:||1) Sporadic or NF1 associated high-grade malignant peripheral nerve sheath tumors (MPNSTs), not previously treated with chemotherapy for this malignancy. Diagnostic criteria for NF1 are listed in Appendix 3. Unresectable or metastatic MPNST or potentially resectable MPNST for which neoadjuvant chemotherapy is determined to be the best treatment option by the institutional PI. Patients must have either a stage III (AJCC TNM staging system, Appendix 1) or stage IV (metastatic) tumor.|
2) (cont. from # 1) Patients must have measurable disease, defined as at least one tumor that is measurable in two dimensions on CT or MRI scan. Patients who develop a recurrence or progression (WHO criteria) of an MPNST in a previously radiated field may be enrolled if it has been at least 4 weeks since the last dose of radiation therapy. Patients who previously received radiation and develop a local or metastatic recurrence outside of the radiation field are also eligible.
3) Children and adults will be eligible with no upper or lower age limit.
4) Normal cardiac function (ejection fraction by MUGA or ECHO that is within institutional normal range)
5) Normal Serum creatinine for age or creatinine clearance > 60ml/min/1.73m2. Age < or = 5 years, creatinine should be < or = 0.8. Age > 5 yrs but < or = to 10 years, creatinine should be < or = 1.0. Age > 10 years but < or = 15 years, creatinine should be < or = 1.2. Age > 15 years, creatinine should be within institutional normal limits.
6) Adequate liver function (SGPT < 5 x the upper limit of normal and bilirubin < 2.5 x the upper limit of normal).
7) Normal unsupported hematologic function (absolute neutrophil count > or = 1500 microliters, hemoglobin > or = 9.0 g/dl and platelet count > or = 100,000 microliters).
8) Subjects of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study.
9) Patients who have received treatment for other malignancies or other conditions such as plexiform neurofibroma or optical pathway tumor, or other NF1 associated tumor in the past with biologic agents or chemotherapy may be eligible, provided they have recovered from toxicities of prior treatment to meet all eligibility criteria, but should be discussed with the PI to determine eligibility.
10) ECOG performance status of 0,1, or 2. Clinical Status - 0 is Asymptomatic, 1 is Symptomatic and fully ambulatory, 2 is Symptomatic, in bed < 50% of the day, 3 is Symptomatic, in bed > 50% of the day but not bedridden, and 4 is Bedridden.
11) Informed Consent: Diagnostic or laboratory studies performed exclusively to determine eligibility for this trial must only be done after obtaining written informed consent from all patients or their legal guardians (if the patient is < 18 years old). This can be accomplished through an IRB-approved institutional screening protocol or the study specific protocol. Documentation of the informed consent for screening will be maintained in the patient's research chart.
12) (cont. from #12) Studies or procedures that were performed for clinical indications (not exclusively to determine eligibility) may be used for baseline values even if the studies were done before informed consent was obtained. An age appropriate assent form for children from 13 through 17 years was developed, and a one page information sheet for children from 7 through 12 years.