Publication
Phase I dose-finding study of vandetanib in combination with gemcitabine in locally advanced unresectable or metastatic pancreatic adenocarcinoma
Journal Paper/Review - Sep 15, 2011
Saletti Piercarlo, Sessa Cristiana, De Dosso Sara, Cerny Thomas, Renggli Verena, Köberle Dieter
Units
PubMed
Doi
Citation
Type
Journal
Publication Date
Issn Electronic
Pages
Brief description/objective
OBJECTIVES
Vandetanib is an oral inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor and RET (REarranged during Transfection) signaling. The primary objective of this open-label phase I trial was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of vandetanib in combination with gemcitabine in patients with unresectable, locally advanced or metastatic pancreatic adenocarcinoma (PAC).
METHODS
Patients received vandetanib (100 or 300 mg/day) plus gemcitabine (1,000 mg/m(2) i.v. on days 1, 8 and 15 per 28-day cycle) until disease progression, unacceptable toxicity or withdrawal of patient consent. The MTD was determined by the assessment of dose-limiting toxicity (DLT) during the first 28 days of treatment.
RESULTS
Fifteen patients were treated. No DLTs occurred in the first cohort of vandetanib 100 mg (n = 3) and recruitment continued at the 300-mg dose level. At the 300-mg dose, 3 out of 12 patients (including 2 in the expansion cohort) experienced DLTs (aphasia, elevated liver enzymes and neutropenia; all of them grade 3), thus exceeding the MTD. No objective responses were observed, with stable disease being the best response in 78% of evaluable patients.
CONCLUSIONS
Vandetanib 100 mg/day is the RD in combination with gemcitabine in the treatment of patients with advanced PAC.