title: Docetaxel/Gemcitabine followed by gemcitabine and external beam radiotherapy in patients with pancreatic adenocarcinoma.
abstract: BACKGROUND
  Pancreatic cancer remains highly lethal. Previous attempts with neoadjuvant therapy in this disease have been inconclusive, but a potential for benefit exists. We conducted a phase II trial of dose-intense docetaxel and gemcitabine followed by twice-weekly gemcitabine and external beam radiotherapy in patients with pancreatic adenocarcinoma.
  
  
  METHODS
  Patients with stage I to III disease were eligible. Docetaxel 65 mg/m(2) intravenously over 1 hour and gemcitabine 4000 mg/m(2) given intravenously over 30 minutes were given on days 1, 15, and 29. On day 43, radiotherapy was begun at 50.4 Gy with gemcitabine 50 mg/m(2) intravenously over 30 minutes twice weekly for 12 doses. After treatment, patients were considered for resection.
  
  
  RESULTS
  Twenty-four assessable patients were recruited onto the trial. All but one patient completed a full 12 weeks of therapy. Grade 3 and 4 hematological and nonhematological toxicities were common but manageable, and neutropenic fever did not occur. No patient had local tumor progression. Twelve patients (50%) responded by Response Evaluation Criteria in Solid Tumors Group (RECIST) criteria, including one radiographic complete response. Seventeen patients underwent resection after therapy. Margin-negative resections were performed in 13 patients, including 9 patients whose disease was borderline or unresectable before treatment. A treatment effect was seen in all resection specimens. There have been no local recurrences of tumor, and several patients remain alive without evidence of disease.
  
  
  CONCLUSIONS
  Docetaxel/gemcitabine followed by gemcitabine/radiotherapy is active in the treatment of pancreatic adenocarcinoma, with manageable toxicity. Tumor downstaging occurs in some patients to allow complete resection. Further investigation of this regimen is warranted.
authors.affiliation: Gastrointestinal Oncology Program, Dartmouth-Hitchcock Medical Center/Norris Cotton Cancer Center, One Medical Center Drive, Lebanon, NH 03756, USA. j.marc.pipas@hitchcock.org
authors.forename: J Marc
authors.initials: JM
authors.lastname: Pipas
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Barth
authors.forename: Bassem
authors.initials: B
authors.lastname: Zaki
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Tsapakos
authors.forename: Arief A
authors.initials: AA
authors.lastname: Suriawinata
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bettmann
authors.forename: Justin M
authors.initials: JM
authors.lastname: Cates
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Ripple
authors.forename: John E
authors.initials: JE
authors.lastname: Sutton
authors.forename: Stuart R
authors.initials: SR
authors.lastname: Gordon
authors.forename: Carol E
authors.initials: CE
authors.lastname: McDonnell
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Perez
authors.forename: Nancy
authors.initials: N
authors.lastname: Redfield
authors.forename: Louise P
authors.initials: LP
authors.lastname: Meyer
authors.forename: John F
authors.initials: JF
authors.lastname: Marshall
authors.forename: Bernard F
authors.initials: BF
authors.lastname: Cole
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Colacchio
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077143:Docetaxel; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D020266:Radiotherapy, Conformal; D043823:Taxoids / Q000008:administration & dosage*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000093542:Gemcitabine