The goal of this clinical research study is to learn how different doses of fosaprepitant may effect how ifosfamide-based chemotherapy is absorbed by the body. Researchers also want to learn if fosaprepitant can help to control or prevent delayed nausea and/or vomiting that may be caused by chemotherapy. The safety of this drug will also be studied.

Fosaprepitant is designed to block the natural substance in the brain that causes nausea and vomiting. This may help to prevent and/or control nausea and vomiting caused by chemotherapy.

Study Groups:

If you are found to be eligible to take part in this study, you will receive fosaprepitant during 21-day chemotherapy cycles. You will be randomly assigned (as in a toss of dice) to 1 of 2 study groups, each with 2 divisions:

• If you are in Group A1, you will receive fosaprepitant on Day 1 of Cycle 1.
• If you are in Group A2, you will receive fosaprepitant on Day 1 of Cycle 2.
• If you are in Group B1, you will receive fosaprepitant on Days 1 and 4 of Cycle 1.
• If you are in Group B2, you will receive fosaprepitant on Days 1 and 4 Cycle 2.

You and the study staff will know to which group and division you are assigned. Each time you receive the drug, you will receive it by vein over about 20-30 minutes.

You will also receive the ifosfamide-based chemotherapy prescribed by your doctor, as well as standard drugs for preventing nausea and vomiting (such as ondansetron, lorazepam, diphenhydramine, and promethazine). You will sign a separate consent form that will describe these treatments in detail, along with their risks.

You will receive dexamethasone before chemotherapy, every day for 5 days, to help prevent nausea and vomiting.

Before each chemotherapy cycle, you will be given a study diary. Each day, you will record any side effects you may . You should bring your study diary to every study visit so the study staff can review it.

Study Visits:

Before each cycle that you receive fosaprepitant, the following tests and procedures will be performed:

• You will have a physical exam.
• Your vital signs, weight, and performance status will be recorded.
• You will fill out the same questionnaire you did at screening.
• You will be asked about any other drugs you may be taking. Be sure to tell the study doctor about all drugs (including vitamins, herbal products, and nutritional supplements), because some drugs/substances will cause side effects when taken at the same time as fosaprepitant.
• Blood (about 5 teaspoons) will be drawn for routine tests.

Blood (about 1 teaspoon) will also be drawn 2 times each week during Cycles 1 and 2 for routine tests.

Pharmacokinetic Testing:

On Days 1 and 4 of Cycles 1 and 2 of chemotherapy, blood samples (about 2 teaspoons each time) will be drawn for pharmacokinetic (PK) testing, when possible. PK testing measures the amount of study drug in the body at different time points. The blood will be drawn before you receive ifosfamide, at the end of the infusion, and 4 more times in the 24 hours after the infusion.

Length of Study:

You may receive up to 6 cycles of chemotherapy (and up to 5 cycles of fosaprepitant). You will no longer be able to take the study drug if the disease gets worse or if intolerable side effects occur.

Your participation on the study will be over once you have completed the end-of-study visit.

End-of-Study Visit:

About 3 weeks after your last dose of fosaprepitant, you will return for an end-of-study visit. At this visit, the following tests and procedures will be performed:

• You will have a physical exam.
• Your vital signs, weight, and performance status will be recorded.
• You will fill out the same questionnaire you did at screening.
• You will be asked about any other drugs you may be taking.
• Blood (about 5 teaspoons) will be drawn for routine tests.

This is an investigational study. Fosaprepitant is FDA approved and commercially available in combination with other drugs for the prevention of nausea and vomiting that may be caused by chemotherapy. It is investigational to study how fosaprepitant may affect the drug levels of ifosfamide in the blood and how many doses should be given.

Up to 36 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients with sarcoma which is locally advanced, at high risk for relapse or metastatic for whom treatment with doxorubicin plus ifosfamide (AI) or AI and vincristine (VAI) is indicated.
2. Must be 18-65 years of age.
3. Male and Females of child bearing potential must use acceptable methods of birth control which include oral contraceptives, spermicide with either a condom, diaphragm or cervical cap, us of a intrauterine device (IUD) or abstinence.
4. Adequate hematologic (ANC >/= 1500/mm^3, platelet count >/= 100,000/mm^3), renal (serum creatinine </= 1.5 mg/dL), hepatic (serum bilirubin count </= 1.5 x normal and SGOT or SGPT </= 3 x normal) functions.
5. Karnofsky Performance Status >/= 60%
6. Signed informed consent form.
7. Patients are required to read and understand English to comply with protocol requirements.

Exclusion Criteria:

1. Pregnant or lactating women.
2. Patients with any co-morbid condition which renders patients at high risk of treatment complication.
3. Known allergy to fosaprepitant or any of its active components.
4. Patient has uncontrolled angina, congestive heart failure (New York Heart Association > class II or known ejection fraction < 40%), uncontrolled cardiac arrhythmia or hypertension, or acute myocardial infarction within 3 months.
5. Patient has an active seizure disorder. (Patients with a previous history of seizure disorders will be eligible for the study, if they have had no evidence of seizure activity, and they have been free of antiseizure medication for the previous 5 years).
6. Prior surgery or radiotherapy (RT) within 2 weeks of study entry.
7. Psychological, social, familial, or geographical reasons that would prevent scheduled visits and follow-up.
8. Patients receiving any medication for pre-existing nausea/vomiting will be excluded.