title: Phase I trial of intratumoral injection of an adenovirus encoding interleukin-12 for advanced digestive tumors.
abstract: OBJECTIVE
  To evaluate the feasibility and safety of intratumoral injection of an adenoviral vector encoding human interleukin-12 genes (Ad.IL-12) and secondarily, its biologic effect for the treatment of advanced digestive tumors.
  
  
  METHODS
  Ad.IL-12 was administered in doses ranging from 2.5 x 10(10) to 3 x 10(12) viral particles, to seven cohorts of patients with advanced pancreatic, colorectal, or primary liver malignancies. Patients were thoroughly assessed for toxicity, and antitumor response was evaluated by imaging techniques, tumor biopsy, and hypersensitivity skin tests. Patients with stable disease and no serious adverse reactions were allowed to receive up to 3 monthly doses of Ad.IL-12.
  
  
  RESULTS
  Twenty-one patients (nine with primary liver, five with colorectal, and seven with pancreatic cancers) received a total of 44 injections. Ad.IL-12 was well tolerated, and dose-limiting toxicity was not reached. Frequent but transient adverse reactions, including fever, malaise, sweating, and lymphopenia, seemed to be related to vector injection rather than to transgene expression. No cumulative toxicity was observed. In four of 10 assessable patients, a significant increase in tumor infiltration by effector immune cells was apparent. A partial objective remission of the injected tumor mass was observed in a patient with hepatocellular carcinoma. Stable disease was observed in 29% of patients, mainly those with primary liver cancer.
  
  
  CONCLUSIONS
  Intratumoral injection of up to 3 x 10(12) viral particles of Ad.IL-12 to patients with advanced digestive malignancies is a feasible and well-tolerated procedure that exerts only mild antitumor effects.
authors.affiliation: Liver Unit, Division of Gene Therapy, Department of Internal Medicine, Clinica Universitaria, University of Navarre, Ap. 4209 Pamplona 31080, Spain. bsangro@unav.es
authors.forename: Bruno
authors.initials: B
authors.lastname: Sangro
authors.forename: Guillermo
authors.initials: G
authors.lastname: Mazzolini
authors.forename: Juan
authors.initials: J
authors.lastname: Ruiz
authors.forename: Maite
authors.initials: M
authors.lastname: Herraiz
authors.forename: Jorge
authors.initials: J
authors.lastname: Quiroga
authors.forename: Ignacio
authors.initials: I
authors.lastname: Herrero
authors.forename: Alberto
authors.initials: A
authors.lastname: Benito
authors.forename: Javier
authors.initials: J
authors.lastname: Larrache
authors.forename: Jesus
authors.initials: J
authors.lastname: Pueyo
authors.forename: Jose Carlos
authors.initials: JC
authors.lastname: Subtil
authors.forename: Cristina
authors.initials: C
authors.lastname: Olagüe
authors.forename: Josu
authors.initials: J
authors.lastname: Sola
authors.forename: Belén
authors.initials: B
authors.lastname: Sádaba
authors.forename: Carlos
authors.initials: C
authors.lastname: Lacasa
authors.forename: Ignacio
authors.initials: I
authors.lastname: Melero
authors.forename: Cheng
authors.initials: C
authors.lastname: Qian
authors.forename: Jesus
authors.initials: J
authors.lastname: Prieto
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000628:therapy; D004067:Digestive System Neoplasms / Q000628:therapy*; D005240:Feasibility Studies; D005260:Female; D015316:Genetic Therapy / Q000009:adverse effects; D006801:Humans; D015552:Injections, Intralesional; D018664:Interleukin-12 / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000628:therapy
chemical_list: D018664:Interleukin-12