title: Phase I study of daily irinotecan as a radiation sensitizer for locally advanced pancreatic cancer.
abstract: OBJECTIVE
  The study aimed to determine the maximum tolerated dose of daily irinotecan given with concomitant radiotherapy in patients with locally advanced adenocarcinoma of the pancreas.
  
  
  METHODS
  Between September 2000 and March 2008, 36 patients with histologically proven unresectable pancreas adenocarcinoma were studied prospectively. Irinotecan was administered daily, 1 to 2 h before irradiation. Doses were started at 6 mg/m(2) per day and then escalated by increments of 2 mg/m(2) every 3 patients. Radiotherapy was administered in 2-Gy fractions, 5 fractions per week, up to a total dose of 50 Gy to the tumor volume. Inoperability was confirmed by a surgeon involved in a multidisciplinary team. All images and responses were centrally reviewed by radiologists.
  
  
  RESULTS
  Thirty-six patients were enrolled over a period of 8 years through eight dose levels (6 mg/m(2) to 20 mg/m(2) per day). The maximum tolerated dose was determined to be 18 mg/m(2) per day. The dose-limiting toxicities were nausea/vomiting, diarrhea, anorexia, dehydration, and hypokalemia. The median survival time was 12.6 months with a median follow-up of 53.8 months. The median progression-free survival time was 6.5 months, and 4 patients (11.4%) with very good responses could undergo surgery.
  
  
  CONCLUSIONS
  The maximum tolerated dose of irinotecan is 18 mg/m(2) per day for 5 weeks. Dose-limiting toxicities are mainly gastrointestinal. Even though efficacy was not the aim of this study, the results are very promising, with a median survival time of 12.6 months.
authors.affiliation: Department of Medical Oncology, University of Lyon-Centre Léon Bérard, Lyon, France. delafo@lyon.fnclcc.fr
authors.forename: Christelle
authors.initials: C
authors.lastname: de la Fouchardière
authors.forename: Sylvie
authors.initials: S
authors.lastname: Négrier
authors.forename: Hugues
authors.initials: H
authors.lastname: Labrosse
authors.forename: Isabelle
authors.initials: I
authors.lastname: Martel Lafay
authors.forename: Françoise
authors.initials: F
authors.lastname: Desseigne
authors.forename: Pierre
authors.initials: P
authors.lastname: Méeus
authors.forename: David
authors.initials: D
authors.lastname: Tavan
authors.forename: Fabien
authors.initials: F
authors.lastname: Petit-Laurent
authors.forename: Michel
authors.initials: M
authors.lastname: Rivoire
authors.forename: David
authors.initials: D
authors.lastname: Pérol
authors.forename: Christian
authors.initials: C
authors.lastname: Carrie
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D011446:Prospective Studies; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016019:Survival Analysis
chemical_list: D011838:Radiation-Sensitizing Agents; D000077146:Irinotecan; D002166:Camptothecin