Multicenter Prospective Phase II Study for Neoadjuvant S-1 and Concurrent Radiotherapy for Borderline Resectable Pancreatic Cancer

RATIONALE: Borderline resectable pancreatic cancer is frequently related to a positive surgical margin and has a poor prognosis after resection. Neoadjuvant chemoradiation with intensive local effect may lead to substantial local control and prolongation of survival in borderline resectable pancreatic cancer.

PURPOSE: This phase II trial assess efficacy and safety of neoadjuvant S-1 and concurrent radiotherapy for borderline resectable pancreatic cancer.

S-1: S-1 is an oral fluorinated pyrimidine agent which contains tegafur (FT, a prodrug of 5-FU), 5-chloro-2,4-dihydropyrimidine (CHDP) and potassium oxonate (Oxo) effective for gastric and various other types of cancers. S-1 is also active for pancreatic cancer: S-1 demonstrated non-inferiority to gemcitabine in overall survival for metastatic or locally advanced pancreatic cancer (LAPC).

S-1 and Concurrent radiotherapy: S-1 therapy with concurrent radiation therapy (RT) had favorable activity with overall tumor response rate of 37%, as well as mild toxicity in patients with LAPC. The median survival time and the 2-year survival rate for LAPC patients treated by S-1/RT were 16.2 months and 26% respectively.

Definition of Borderline Resectable Pancreatic Cancer:(1) Reconstructible bilateral impingement of superior mesenteric vein or portal vein; (2) Tumor contact with the superior mesenteric artery (SMA) of \

Inclusion Criteria:

• Cytologic or histologic proof of pancreatic ductal carcinoma or adenosquamous carcinoma is required prior to study entry.

• Disease assessment by Multi Detector-row Computed Tomography (MDCT) scan within 2 weeks of study entry

• Borderline resectable pancreatic cancer

• No evidence of metastatic disease as determined by chest CT scan, and abdominal CT scan and laparoscopy. Paraaortic lymph node metastasis is considered as metastatic.

• Age >/=20 years old, </=75 years old

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• No prior chemotherapy or radiotherapy for pancreatic cancer

• A square 10 x 10 cm radiation field could encompass all pancreatic lesions and lymph node metastases

• Adequate oral intake

• Appropriate biliary drainage for obstructive jaundice

• Lab Values:

  • hemoglobin concentration >/= 9.0 g/dL
  • leukocyte count >/= 3,000/mm3
  • platelet count >/= 100,000/mm3
  • serum total bilirubin </= 2.0 mg dL, or </=3.0 mg/dL with biliary drainage
  • Aspartate Transaminase (AST) and Alanine Transaminase (ALT) </= 100 U/L, or </= 150 U/L with biliary drainage
  • serum albumin >/= 3.0 g/dl
  • serum creatinine </= 1.2 mg dL
  • Creatinine clearance >/= 50 ml/min

• Written informed consent

Exclusion Criteria:

• Tumor invasion to the alimentary tract determined by abdominal CT scan or endoscopic examination
• Prior chemotherapy using fluoropyrimidine
• Prior radiation therapy to the abdomen
• Watery diarrhea
• Concurrent phenytoin, warfarin potassium, or flucytosine treatment
• Presence of contrast medium allergy
• Pulmonary fibrosis or interstitial pneumonia
• Pleural effusion or ascites
• Active infection
• Uncontrolled diabetes mellitus (FBS >/= 200mg/dL or HbA1c >/= 10.0)
• Active concomitant malignancy
• Active gastroduodenal ulcer
• Severe complications such as cardiac or renal disease
• Regular administration of systemic corticosteroid
• Psychiatric disorder
• History of drug hypersensitivity
• Pregnant and lactating women and women of childbearing age who were not using effective contraception