Neoadjuvant S-1 and Concurrent Radiotherapy for Borderline Resectable Pancreatic Cancer
Neoadjuvant S-1 and Concurrent Radiotherapy for Borderline Resectable Pancreatic Cancer
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 </= 180 degrees ; (3) Tumor contact with the common hepatic artery
 of </= 180 degrees (at the root of the gastroduodenal artery); and (4) Tumor contact with the
 celiac axis of </= 180 degrees.

 Tumor with portal vein tumor thrombus and tumor contact with the second or further jejunal
 SMA branch are considered as unresectable. Tumor which is contact with the common hepatic
 artery or celiac axis but can be resected by distal pancreatectomy with en bloc celiac axis
 resection, is not included in this study.
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