title: Phase II study of induction fixed-dose rate gemcitabine and bevacizumab followed by 30 Gy radiotherapy as preoperative treatment for potentially resectable pancreatic adenocarcinoma.
abstract: BACKGROUND
  Eighty percent of patients with resected pancreatic ductal carcinoma (PDC) experience treatment failure within 2 years. We hypothesized that preoperative fixed-dose rate (FDR) gemcitabine (GEM) combined with the angiogenesis inhibitor bevacizumab (BEV) and accelerated 30 Gy radiotherapy (RT) would improve outcomes among patients with potentially resectable PDC.
  
  
  METHODS
  This phase II trial tested induction FDR GEM (1,500 mg/m(2)) plus BEV (10 mg/kg IV) every 2 weeks for three cycles followed by accelerated RT (30 Gy in 10 fractions) plus BEV directed at gross tumor volume plus a 1-2 cm vascular margin. Subjects underwent laparoscopy and resection after day 85. Therapy was considered effective if the complete pathologic response rate exceeded 10 % and the margin-negative resection rate exceeded 80%.
  
  
  RESULTS
  Fifty-nine subjects were enrolled; 29 had potential portal vein involvement. Two grade 4 (3.4%) and 19 grade 3 toxicities (32.8%) occurred. Four subjects manifested radiographic progression, and 10 had undetected carcinomatosis. Forty-three pancreatic resections (73%) were performed, including 19 portal vein resections (44%). Margin-negative outcomes were observed in 38 (88%, 95% confidence interval [CI] 75-96), with one complete pathologic response (2.3%; 95% CI 0.1-12). There were seven (6 grade 3; 1 grade 4) wound complications (13%). Median overall survival for the entire cohort was 16.8 months (95% CI 14.9-21.3) and 19.7 months (95% CI 16.5-28.2) after resection.
  
  
  CONCLUSIONS
  Induction therapy with FDR GEM and BEV, followed by accelerated BEV/RT to 30 Gy, was well tolerated. Although both effectiveness criteria were achieved, survival outcomes were equivalent to published regimens.
authors.affiliation: Division of Surgical Oncology, UPMC Pancreatic Cancer Center, Pittsburgh, PA, USA.
authors.forename: George
authors.initials: G
authors.lastname: Van Buren
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ramanathan
authors.forename: Alyssa M
authors.initials: AM
authors.lastname: Krasinskas
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Smith
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Abood
authors.forename: Nathan
authors.initials: N
authors.lastname: Bahary
authors.forename: Barry C
authors.initials: BC
authors.lastname: Lembersky
authors.forename: Yongli
authors.initials: Y
authors.lastname: Shuai
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Potter
authors.forename: David L
authors.initials: DL
authors.lastname: Bartlett
authors.forename: Amer H
authors.initials: AH
authors.lastname: Zureikat
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Zeh
authors.forename: A James
authors.initials: AJ
authors.lastname: Moser
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D010535:Laparoscopy; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011300:Preoperative Care; D011379:Prognosis; D011879:Radiotherapy Dosage; D012074:Remission Induction; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000068258:Bevacizumab; D000093542:Gemcitabine