The goal of this clinical research study is to compare 2 treatment schedules of Aloxi (palonosetron) in patients with sarcoma who are receiving chemotherapy with adriamycin and ifosfamide. The safety of the drug and schedules will be studied. The effect of palonosetron on patients' quality of life (QOL) will also be studied.

Palonosetron is a drug that is designed to prevent and treat nausea and vomiting that is caused by chemotherapy.

If you are found to be eligible to take part in this study, you will have several blood samples taken (about 3 teaspoons each). Researchers will use the samples to monitor blood counts during chemotherapy and periods of myelosuppression (a condition in which bone marrow activity is decreased). These blood samples will be taken at least 2 times a week, and at certain times, they will be taken once a day. You will be asked to fill out a QOL questionnaire about nausea and vomiting, at least 2 times during Cycle 1 (one cycle lasts 21 days). It will take about 10 minutes to complete the questionnaire.

You will be randomly assigned (as in the toss of a coin) to one of two treatment groups. Participants in one group will receive one dose of palonosetron on Day 0. Participants in the other group will receive 3 doses of palonosetron on Days 0, 2, and 4. Palonosetron will be given to participants in both groups, as an intravenous (IV--through a needle in your vein) infusion over 30 minutes.

You will be asked to keep a study diary during the treatment period. Study personnel will give you the diary and tell you how to complete it. Your side effects (including how severe they are) and medication doses need to be recorded in your diary every day. You will be asked to return your diary at each post-treatment return visit (about every 3 weeks).

While you are on this study, you will receive chemotherapy as part of your standard treatment. All participants will receive at least 2 cycles of adriamycin and ifosfamide chemotherapy (AI). A cycle is 3 weeks long. You may receive up to 6 cycles of adriamycin and ifosfamide. Adriamycin will be given as one large injection through a central venous catheter (plastic tube and needle placed under the collarbone) on Day 0. Ifosfamide will be given over 3 hours every day for 4 days (Days 0-3). Zinecard will be given as one large injection through the catheter on Day 0. Mesna will be given as a 24-hour infusion every day for 4 days through the same catheter (Days 0-3). Zinecard and mesna are given as standard of care. Zinecard is used to protect against heart-related side effects. Mesna is used to protect against bladder-related side effects. For patients with certain types of sarcoma, vincristine will be given through the catheter by rapid infusion on Day 0 only.

You may be treated as an outpatient or an inpatient. You will be asked to return to M. D.Anderson every 3 weeks for evaluation of your disease, by having a chest x-ray, a computerized tomography (CT) scan, a magnetic resonance imaging (MRI) scan, and a physical exam performed. Additional blood samples (about 3 teaspoons) will be taken before each cycle and as often as needed to measure your blood counts and electrolytes (minerals in the body) to monitor any imbalances.

You will be asked to contact the study doctor or nurse about any bad side effects you experience or any medications (over-the-counter or prescription) you take during the treatment period. You will also be asked to notify your other doctors (separate from the study doctors) that you are participating in this research study.

Your treatment will continue for at least 6 cycles, unless your disease gets worse or you experience intolerable side effects. If you experience any intolerable side effects or your disease gets worse while on this study, you may be taken off this study.

Once you stop treatment, you will have what is called an end-of-study visit. During this visit, you will be evaluated for your disease status with CT and MRI scans. You will have your vital signs and weight measured. You will be asked about any medications you have taken since your last visit and any bad side effects that you have experienced. You will also have a final blood draw (about 3 teaspoons) for routine tests.

Your participation in this study should end at about 18 weeks (4 to 5 months).

Once you go off this study, you will have standard follow-up as is required by your doctor.

This is an investigational study. Palonosetron is FDA approved and is commercially available.

Up to 50 patients will take part in this study. All will be enrolled at M. D. Anderson.

Inclusion Criteria:

• Patients with sarcoma which is locally advanced, at high risk for relapse or metastatic for whom treatment with AI is indicated.
• Must be between the ages of 18 and 65 years of age.
• Patients with childbearing potential (defined as not post menopausal for 12 months or no previous surgical sterilization) must use adequate birth control.
• Adequate hematologic (Absolute neutrophil count (ANC)>/= 1500/mm^3, >/= hemoglobin (Hgb, Hb) 10gm/dL, platelet count >/= 150,000/mm^3), renal (serum creatinine </= 1.5 mg/dL), hepatic (serum bilirubin count </= 1.5 * normal and Serum glutamic pyruvic transaminase (SGPT) <3 * normal) functions.
• Karnofsky Performance Status >/= 80.
• Signed informed consent form.

Exclusion Criteria:

• Pregnant or lactating women.
• Patients with comorbid condition which renders patients at high risk of treatment complication.
• Patients with symptomatic or untreated metastatic disease to CNS.
• Patients with significant cardiac disease (New York Heart Association (NYHA) Class III or IV), arrhythmia, or recent history of Myocardial infarction (MI) or ischemia.
• Patients with known hypersensitivity to 5-HT3 antagonists.
• Any vomiting or >/= grade 2 nausea in the 24 hours preceding chemotherapy.
• Ongoing vomiting from any organic etiology.
• Radiotherapy within 2 weeks of study entry.