Phase I study of daily irinotecan as a radiation sensitizer for locally advanced pancreatic cancer.
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.
de la Fouchardière
Christelle
C
Department of Medical Oncology, University of Lyon-Centre Léon Bérard, Lyon, France. delafo@lyon.fnclcc.fr
Négrier
Sylvie
S
Labrosse
Hugues
H
Martel Lafay
Isabelle
I
Desseigne
Françoise
F
Méeus
Pierre
P
Tavan
David
D
Petit-Laurent
Fabien
F
Rivoire
Michel
M
Pérol
David
D
Carrie
Christian
C
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
D011838:Radiation-Sensitizing Agents; D000077146:Irinotecan; D002166:Camptothecin