title: Gemcitabine and ISIS-2503 for patients with locally advanced or metastatic pancreatic adenocarcinoma: a North Central Cancer Treatment Group phase II trial.
abstract: OBJECTIVE
  Gemcitabine remains the standard therapy for metastatic pancreatic adenocarcinoma (ACA), but has limited activity. ISIS-2503 is an antisense compound directed against H-ras with preclinical activity against pancreatic ACA in tumor models. The combination of ISIS-2503 and gemcitabine has been evaluated in a prior phase I study.
  
  
  METHODS
  Patients with metastatic or locally advanced pancreatic ACA not amenable to surgery or local radiation received gemcitabine 1,000 mg/m(2) intravenously over 30 minutes on days 1 and 8 and ISIS-2503 6 mg/kg/d as a continuous intravenous infusion over 14 days of an every-3-weeks cycle. Responses were monitored by radiologic imaging every 6 weeks.
  
  
  RESULTS
  Forty-eight eligible patients were enrolled, 43 with metastatic disease. Median follow-up was 12.6 months (range, 2.2 to 16.8 months) for living patients. A median of four cycles of treatment was given (range, 1 to 18 cycles). All patients were assessable for response and toxicity. The 6-month survival percentage was 57.5% (95% CI, 44.9% to 73.5%) and the median survival was 6.6 months. The response rate was 10.4% (one complete response, four partial responses). Clinically significant toxicity was limited except for one fatal pulmonary embolism.
  
  
  CONCLUSIONS
  This study shows a promising response rate to the combination of gemcitabine and ISIS-2503 in patients with pancreatic ACA. The observed 6-month survival rate in these patients met our protocol-defined criteria for success. This regimen is tolerable, but is of unclear benefit. Additional studies evaluating the role of gemcitabine and ISIS-2503 in the treatment of pancreatic ACA should be considered.
authors.affiliation: Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. alberts.steven@mayo.edu
authors.forename: Steven R
authors.initials: SR
authors.lastname: Alberts
authors.forename: Mark
authors.initials: M
authors.lastname: Schroeder
authors.forename: Charles
authors.initials: C
authors.lastname: Erlichman
authors.forename: Preston D
authors.initials: PD
authors.lastname: Steen
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Foster
authors.forename: Dennis F
authors.initials: DF
authors.lastname: Moore
authors.forename: Kendrith M
authors.initials: KM
authors.lastname: Rowland
authors.forename: Suresh
authors.initials: S
authors.lastname: Nair
authors.forename: Loren K
authors.initials: LK
authors.lastname: Tschetter
authors.forename: Tom R
authors.initials: TR
authors.lastname: Fitch
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D054735:Phosphorothioate Oligonucleotides; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; C122000:ISIS 2503; D016376:Oligonucleotides, Antisense; D054735:Phosphorothioate Oligonucleotides; D003841:Deoxycytidine; D000093542:Gemcitabine