Phase I study of daily irinotecan as a radiation sensitizer for locally advanced pancreatic cancer.

Abstract

PURPOSE:

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 AND MATERIALS:

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: Christelle de la Fouchardière, Sylvie Négrier, Hugues Labrosse, Isabelle Martel Lafay, Françoise Desseigne, Pierre Méeus, David Tavan, Fabien Petit-Laurent, Michel Rivoire, David Pérol, Christian Carrie
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 77 Issue 2 Pg. 409-13 (Jun 01 2010) ISSN: 1879-355X [Electronic] United States
• PMID: 20116933 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Radiation-Sensitizing Agents
• Irinotecan
• Camptothecin

Topics

• Adenocarcinoma (pathology, radiotherapy)
• Adult
• Aged
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives)
• Disease Progression
• Drug Administration Schedule
• Feasibility Studies
• Female
• Humans
• Irinotecan
• Male
• Maximum Tolerated Dose
• Middle Aged
• Pancreatic Neoplasms (mortality, pathology, radiotherapy, surgery)
• Prospective Studies
• Radiation-Sensitizing Agents (administration & dosage, adverse effects)
• Survival Analysis