Stereotactic Radiation Therapy and Combination Chemotherapy in Treating Patients Undergoing Surgery for Locally Advanced Pancreatic Cancer

OBJECTIVES:

Primary

• Determine the clinical response rate in patients undergoing surgery for locally advanced pancreatic cancer treated with stereotactic radiotherapy, gemcitabine hydrochloride, and oxaliplatin.

Secondary

• Determine the toxicity of this regimen in these patients.
• Determine the time to disease progression in patients treated with this regimen.
• Determine the time to death in patients treated with this regimen.
• Determine perioperative morbidity and mortality in patients treated with this regimen.
• Determine the rate of R0 resections in patients treated with this regimen.
• Determine the histologic response rate in these patients.

OUTLINE:

• Neoadjuvant therapy: Patients undergo hypofractionated, stereotactic radiotherapy on days 1-5. Patients also receive gemcitabine hydrochloride IV over 100 minutes on day 1 and oxaliplatin IV over 120 minutes on day 2. Treatment with gemcitabine hydrocloride and oxaliplatin repeats every 2 weeks for 3 courses.
• Surgery: Patients with resectable disease undergo tumor resection. Patients with unresectable disease undergo a second course of neoadjuvant chemoradiotherapy followed by resection.
• Adjuvant therapy: Beginning 3-4 weeks after surgery, patients receive 3 more courses of chemotherapy as in neoadjuvant therapy.

After completion of study treatment, patients are followed every 3 months for up to 2 years.

PROJECTED ACCRUAL: A total of 29 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas or intrapancreatic bile duct carcinoma

• Overall view of image morphology and CA19-9 (< 500 U/L) demonstrating pancreatic cancer allowed if histologic/cytologic confirmation is unavailable
• Locally advanced disease, meeting 1 of the following criteria:

• Uncertain R0 resectability dependant on relation to portal vein, sinus confluens, superior mesenteric artery, and superior mesenteric vein (e.g., contact with portal vein, superior mesenteric vein, or arterial vessels, but < 180° encasement)
• Unresectable pancreatic cancer (e.g., contact with portal vein, superior mesenteric artery or arterial vessels, > 180° encasement)
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 1 cm by spiral CT scan or MRI

• Patients with no measurable disease may be assessed for feasibility only
• No distant metastases

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-1 OR Karnofsky PS 80-100%
• WBC ≥ 3,000/mm³
• Granulocyte count ≥ 2,000/mm³
• Platelet count ≥ 100,000/mm³
• Creatinine clearance > 30 mL/min
• Bilirubin ≤ 3.0 times upper limit of normal
• AST and ALT ≤ 2.5 times normal
• Alkaline phosphatase ≤ 2.5 times normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No secondary malignancy within the past 5 years that was not curatively treated
• No known intolerance to any of the study drugs
• No preexisting polyneuropathy > grade 1
• No active uncontrolled infection
• No cardiac insufficiency despite optimal medication
• No New York Heart Association class III or IV congestive heart failure
• LVEF ≥ 50% OR shortening fraction ≥ 25%
• No angina pectoris (at rest or under stress) unexplained by interventional cardiology within the past 6 months
• No myocardial infarction within the past 6 months
• No uncontrolled diabetes mellitus
• No other existing serious medical impairments that would preclude study compliance

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy
• No prior radiotherapy to the abdomen