title: A multi-institutional phase 2 study of neoadjuvant gemcitabine and oxaliplatin with radiation therapy in patients with pancreatic cancer.
abstract: BACKGROUND
  The purpose of this study was to evaluate preoperative treatment with full-dose gemcitabine, oxaliplatin, and radiation therapy (RT) in patients with localized pancreatic cancer.
  
  
  METHODS
  Eligibility included confirmation of adenocarcinoma, resectable or borderline resectable disease, a performance status ≤2, and adequate organ function. Treatment consisted of two 28-day cycles of gemcitabine (1 g/m(2) over 30 minutes on days 1, 8, and 15) and oxaliplatin (85 mg/m(2) on days 1 and 15) with RT during cycle 1 (30 Gray [Gy] in 2-Gy fractions). Patients were evaluated for surgery after cycle 2. Patients who underwent resection received 2 cycles of adjuvant chemotherapy.
  
  
  RESULTS
  Sixty-eight evaluable patients received treatment at 4 centers. By central radiology review, 23 patients had resectable disease, 39 patients had borderline resectable disease, and 6 patients had unresectable disease. Sixty-six patients (97%) completed cycle 1 with RT, and 61 patients (90%) completed cycle 2. Grade ≥3 adverse events during preoperative therapy included neutropenia (32%), thrombocytopenia (25%), and biliary obstruction/cholangitis (14%). Forty-three patients underwent resection (63%), and complete (R0) resection was achieved in 36 of those 43 patients (84%). The median overall survival was 18.2 months (95% confidence interval, 13-26.9 months) for all patients, 27.1 months (95% confidence interval, 21.2-47.1 months) for those who underwent resection, and 10.9 months (95% confidence interval, 6.1-12.6 months) for those who did not undergo resection. A decrease in CA 19-9 level after neoadjuvant therapy was associated with R0 resection (P = .02), which resulted in a median survival of 34.6 months (95% confidence interval, 20.3-47.1 months). Fourteen patients (21%) are alive and disease free at a median follow-up of 31.4 months (range, 24-47.6 months).
  
  
  CONCLUSIONS
  Preoperative therapy with full-dose gemcitabine, oxaliplatin, and RT was feasible and resulted in a high percentage of R0 resections. The current results are particularly encouraging, because the majority of patients had borderline resectable disease.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Kim
authors.forename: Edgar
authors.initials: E
authors.lastname: Ben-Josef
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Herman
authors.forename: Tanios
authors.initials: T
authors.lastname: Bekaii-Saab
authors.forename: Laura A
authors.initials: LA
authors.lastname: Dawson
authors.forename: Kent A
authors.initials: KA
authors.lastname: Griffith
authors.forename: Isaac R
authors.initials: IR
authors.lastname: Francis
authors.forename: Joel K
authors.initials: JK
authors.lastname: Greenson
authors.forename: Diane M
authors.initials: DM
authors.lastname: Simeone
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Lawrence
authors.forename: Daniel
authors.initials: D
authors.lastname: Laheru
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Wolfgang
authors.forename: Terence
authors.initials: T
authors.lastname: Williams
authors.forename: Mark
authors.initials: M
authors.lastname: Bloomston
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Moore
authors.forename: Alice
authors.initials: A
authors.lastname: Wei
authors.forename: Mark M
authors.initials: MM
authors.lastname: Zalupski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059186:Chemoradiotherapy, Adjuvant; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: gemcitabine; neoadjuvant; oxaliplatin; pancreatic cancer