A phase I, dose-finding study of sorafenib in combination with gemcitabine and radiation therapy in patients with unresectable pancreatic adenocarcinoma : A Grupo Español Multidisciplinario en Cáncer Digestivo (GEMCAD) study
Aparicio, Jorge (Hospital Universitari i Politècnic La Fe (València))
García-Mora, Carmen (Hospital Universitari i Politècnic La Fe (València))
Martín Flix, Marta (Institut d'Investigació Biomèdica Sant Pau)
Petriz, MªLourdes (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Feliu, Jaime (Hospital Universitario La Paz (Madrid))
Sánchez-Santos, M.E. (Hospital Universitario La Paz (Madrid))
Ayuso Colella, Juan Ramón (Hospital Clínic i Provincial de Barcelona)
Fuster Pelfort, David (Hospital Clínic i Provincial de Barcelona)
Conill, Carlos (Hospital Clínic i Provincial de Barcelona)
Maurel, Joan (Hospital Clínic i Provincial de Barcelona)
Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia

Data:	2014
Resum:	Purpose: Sorafenib, an oral inhibitor of B-raf, VEGFR2, and PDGFR2-beta, acts against pancreatic cancer in preclinical models. Due to the radio-sensitization activity of both sorafenib and gemcitabine, we designed a multicenter, phase I trial to evaluate the safety profile and the recommended dose of this combination used with concomitant radiation therapy. Methods: Patients with biopsy-proven, unresectable pancreatic adenocarcinoma (based on vascular invasion detected by computed tomography) were treated with gemcitabine (300 mg/m2 i. v. weekly x5 weeks) concurrently with radiation therapy (45 Gy in 25 fractions) and sorafenib (escalated doses in a 3+3 design, from 200 to 800 mg/day). Radiation portals included the primary tumor but not the regional lymph nodes. Patients with planning target volumes (PTV) over 500 cc were excluded. Cases not progressing during chemoradiation were allowed to continue with sorafenib until disease progression. Results: Twelve patients were included. Three patients received 200 mg/day, 6 received 400 mg/day, and 3 received 800 mg/day; PTVs ranged from 105 to 500 cc. No dose-limiting toxicities occurred. The most common grade 2 toxicities were fatigue, neutropenia, nausea, and raised serum transaminases. Treatment was discontinued in one patient because of a reversible posterior leukoencephalopathy. There were no treatment-related deaths. Conclusion: The addition of sorafenib to concurrent gemcitabine and radiation therapy showed a favorable safety profile in unresectable pancreatic adenocarcinoma. A dose of 800 mg/day is recommended for phase II evaluation. Trial Registration: EudraCT 2007-003211-31 ClinicalTrials. gov 00789763. © 2014 Aparicio et al.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	PloS one, Vol. 9 Núm. 1 (september 2014) , p. e82209, ISSN 1932-6203

DOI: 10.1371/journal.pone.0082209
PMID: 24416138

6 p, 3.6 MB

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