title: Adenoviral p53 gene transfer and gemcitabine in three patients with liver metastases due to advanced pancreatic carcinoma.
abstract: BACKGROUND
  Current therapies for adenocarcinoma of the pancreas do not improve the life expectancy of patients.
  
  
  METHODS
  In a non-randomized pilot trail we tested whether a local therapy based upon an adenoviral gene transfer of wild type p53 in combination with gemcitabine administration would be safe in patients with liver metastases due to pancreatic carcinoma. We report on the clinical course of three patients with respect to safety, tolerability and tumor response.
  
  
  RESULTS
  Transient grade III toxicities occurred with fever, leucopenia, elevation of AP, ALT, AST, GGT, while grade IV toxicity occurred for bilirubin only. Laboratory tests suggested disseminated intravascular coagulation in all three patients, but fine needle biopsies of liver did not show any histological evidence of thrombus or clot formation. Progression of liver metastases was documented in one and stable disease in another patient two months after treatment. However, a major improvement with regression of the indexed lesion by 80% occurred in a third patient after a single administration of 7.5 x 10(12) viral particles, and time to progression was extended to six months.
  
  
  CONCLUSIONS
  The combination therapy of viral gene transfer and chemotherapy temporarily controls and diminishes tumor burden. Improvement of the toxicity profile is necessary. Further trials are warranted to improve treatment and life expectancy of patients suffering from fatal diseases such as pancreatic carcinoma.
authors.affiliation: Department of Internal Medicine I, Faculty of Medicine Carl Gustav Carus, University of Technology Dresden, Germany. Gernot.Wolkersdoerfer@uniklinikum-dresden.de
authors.forename: Gernot W
authors.initials: GW
authors.lastname: Wolkersdörfer
authors.forename: Christian
authors.initials: C
authors.lastname: Thiede
authors.forename: Rainer
authors.initials: R
authors.lastname: Fischer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Cornelie
authors.initials: C
authors.lastname: Haag