title: Neoadjuvant chemotherapy with gemcitabine and S-1 for resectable and borderline pancreatic ductal adenocarcinoma: results from a prospective multi-institutional phase 2 trial.
abstract: BACKGROUND
  Surgical resection is the only curative strategy for pancreatic ductal adenocarcinoma (PDAC), but recurrence rates are high even after purported curative resection. First-line treatment with gemcitabine and S-1 (GS) is associated with promising antitumor activity with a high response rate. The aim of this study was to assess the feasibility and efficacy of GS in the neoadjuvant setting.
  
  
  METHODS
  In a multi-institutional single-arm phase 2 study, neoadjuvant chemotherapy (NAC) with gemcitabine and S-1, repeated every 21 days, was administered for two cycles (NAC-GS) to patients with resectable and borderline PDAC. The primary end point was the 2-year survival rate. Secondary end points were feasibility, resection rate, pathological effect, recurrence-free survival, and tumor marker status.
  
  
  RESULTS
  Of 36 patients enrolled, 35 were eligible for this clinical trial conducted between 2008 and 2010. The most common toxicity was neutropenia in response to 90% of the relative dose intensity. Responses to NAC included radiological tumor shrinkage (69%) and decreases in CA19-9 levels (89%). R0 resection was performed for 87% in resection, and the morbidity rate (40%) was acceptable. The 2-year survival rate of the total cohort was 45.7%. Patients who underwent resection without metastases after NAC-GS (n = 27) had an increased median overall survival (34.7 months) compared with those who did not undergo resection (P = 0.0017).
  
  
  CONCLUSIONS
  NAC-GS was well tolerated and safe when used in a multi-institutional setting. The R0 resection rate and the 2-year survival rate analysis are encouraging for patients with resectable and borderline PDAC.
authors.affiliation: Division of Gastroenterological Surgery, Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan, fmotoi@surg1.med.tohoku.ac.jp.
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Motoi
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ishida
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Fujishima
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ottomo
authors.forename: Masaya
authors.initials: M
authors.lastname: Oikawa
authors.forename: Takaho
authors.initials: T
authors.lastname: Okada
authors.forename: Hiromune
authors.initials: H
authors.lastname: Shimamura
authors.forename: Shinichi
authors.initials: S
authors.lastname: Takemura
authors.forename: Fuminori
authors.initials: F
authors.lastname: Ono
authors.forename: Masanori
authors.initials: M
authors.lastname: Akada
authors.forename: Kei
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Yu
authors.initials: Y
authors.lastname: Katayose
authors.forename: Shinichi
authors.initials: S
authors.lastname: Egawa
authors.forename: Michiaki
authors.initials: M
authors.lastname: Unno
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D010535:Laparoscopy; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D012074:Remission Induction; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000093542:Gemcitabine