This pilot clinical trial is studying how well aprepitant works in preventing nausea and vomiting in patients undergoing chemotherapy and radiation therapy for pancreatic cancer. Antiemetic drugs, such as aprepitant may help lessen or prevent nausea and vomiting in patients receiving chemotherapy and radiation therapy

PRIMARY OBJECTIVES:

I. Discern the gastrointestinal toxicities associated with 5-FU (fluorouracil)/Gemcitabine (gemcitabine hydrochloride) chemotherapy when combined with upper abdominal radiation therapy.

II. Determine if the addition of prophylactic Aprepitant/5HT-3/Dexamethasone therapy to standard chemoradiation for patients with pancreatic cancer results in less nausea and vomiting when compared to historical controls.

SECONDARY OBJECTIVES:

I. To determine the impact of prophylactic Aprepitant/5HT-3/Dexamethasone therapy on the impact of emesis on daily living, as measured using the MASCC Antiemesis (MAT) tool.

OUTLINE:

CHEMORADIOTHERAPY: Patients undergo radiation therapy once daily on days 1-5 for 5.5 weeks. Patients also receive gemcitabine hydrochloride intravenously (IV) over 30 minutes once weekly and either fluorouracil IV continuously or capecitabine orally (PO) twice daily on days 1-5.

PROPHYLACTIC THERAPY: Beginning 1 hour before chemoradiotherapy, patients receive aprepitant PO on days 1-3. Treatment repeats every 7 days for 5.5 weeks in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION CHEMOTHERAPY: Two to four weeks after completion of chemoradiotherapy and prophylactic therapy, patients without disease progression or a declining performance status receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

Inclusion Criteria:

• Histologic or cytologic diagnosis of carcinoma arising from the pancreas
• Resected or unresectable pancreatic cancer, potentially resectable, or resectable (neoadjuvant) disease (stage II and III); stage IV patients with symptomatic back pain requiring palliation are also eligible at the discretion of the Principal Investigator (PI); resected patients, i.e. - "Whipple" of biliary ductal cancers are also eligible at the discretion of the PI
• Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
• Evidence of disease; this can be measurable, evaluable, or nonmeasurable
• Estimated life expectancy of at least 12 weeks
• Absolute neutrophil (segmented and bands) count (ANC) >= 1.5 X 10^9/L
• Platelets >= 100 X 10^9/L
• Hemoglobin >= 9 g/dL
• Bilirubin =< 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase (AP) =< 3.0 ULN ( AP =< 5 x ULN is acceptable if liver has tumor involvement)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 ULN (AST and ALT =< 5 x ULN is acceptable if liver has tumor involvement)
• Albumin >= 3.0 g/dL
• Signed informed consent from patient
• Male and female patients with reproductive potential must use an approved contraceptive method (e.g., intrauterine device, birth control pills, or barrier device) during and for 3 months after the study

Exclusion Criteria:

• Active infection (at the discretion of the investigator)
• Neuroendocrine tumor of the pancreas
• Documented brain metastasis; brain imaging in symptomatic patients is required to rule out metastases, but not required in asymptomatic patients
• Pregnancy
• Breast feeding
• Serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator)
• Use of any investigational agent within 4 weeks before enrollment into the study
• Significant cardiovascular disease in the form of abnormal electrocardiogram (ECG) coupled with clinical features of recent or recurrent cardiac disease (including myocardial infarction, angina or hypertension)
• Prior treatment with chemotherapy for pancreatic cancer
• Clinically significant effusions (pleural or peritoneal) that cannot be drained