A randomized multi-center phase II trial of the angiogenesis inhibitor Cilengitide (EMD 121974) and gemcitabine compared with gemcitabine alone in advanced unresectable pancreatic cancer
1 Department of General Surgery, University of Heidelberg, Heidelberg, Germany
2 Department of General and Transplantation Surgery, Charité, Virchow-Clinic, Berlin, Germany
3 Department of Hematology and Oncology, Charité, Virchow-Clinic, Berlin, Germany
4 Department of Medicine II, University of Frankfurt Hospital, Frankfurt am Main, Germany
5 Department of Surgery, University Hospital Mannheim, Mannheim, Germany
6 Ludwig Blotzmann-Institute for Applied Cancer Research (LBI-ACR Vienna), Kaiser Franz Josef-Spital, Vienna, Austria
7 Department of Oncology/Hematology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
8 Department of Internal Medicine, Division of Oncology, Medical University of Graz, Graz, Austria
9 Department of Medical Oncology, Oncology Center, Vrije Universiteit Brussel, Brussels, Belgium
10 Department of Gastroenterology, Reinhardt Nieter Krankenhaus, Wilhelmshaven, Germany
11 Department of Medical Oncology, Henri Mondor Hospital, Creteil Cedex, France
12 Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University of Dresden, Dreseden, Germany
13 Department of Internal Medicine I, Division of Clinical Oncology, University Hospital of Vienna, Vienna, Austria
14 Department of Medical Oncology, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK
15 Department of Medicine V, Clinic Darmstadt, Darmstadt, Germany
16 Department of Medicine, Clinic of the City of St. Poelten, St. Pölten, Austria
17 Department of Oncology, University Hospital Antwerpen, Edegem, Belgium
18 Department of Oncology, University Hospital Gent, Gent, Belgium
19 Department of Medicine, St John's Hospital, Chelmsford, Essex, UK
20 Department of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain
21 Department of Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain
22 Department of Pharmacology and Pharmacokinetics, Merck KGaA, Darmstadt, Germany
23 Medical Center of Excellence Oncology, Merck KGaA, Darmstadt, Germany
BMC Cancer 2006, 6:285 doi:10.1186/1471-2407-6-285Published: 11 December 2006
Anti-angiogenic treatment is believed to have at least cystostatic effects in highly vascularized tumours like pancreatic cancer. In this study, the treatment effects of the angiogenesis inhibitor Cilengitide and gemcitabine were compared with gemcitabine alone in patients with advanced unresectable pancreatic cancer.
A multi-national, open-label, controlled, randomized, parallel-group, phase II pilot study was conducted in 20 centers in 7 countries. Cilengitide was administered at 600 mg/m2 twice weekly for 4 weeks per cycle and gemcitabine at 1000 mg/m2 for 3 weeks followed by a week of rest per cycle. The planned treatment period was 6 four-week cycles. The primary endpoint of the study was overall survival and the secondary endpoints were progression-free survival (PFS), response rate, quality of life (QoL), effects on biological markers of disease (CA 19.9) and angiogenesis (vascular endothelial growth factor and basic fibroblast growth factor), and safety. An ancillary study investigated the pharmacokinetics of both drugs in a subset of patients.
Eighty-nine patients were randomized. The median overall survival was 6.7 months for Cilengitide and gemcitabine and 7.7 months for gemcitabine alone. The median PFS times were 3.6 months and 3.8 months, respectively. The overall response rates were 17% and 14%, and the tumor growth control rates were 54% and 56%, respectively. Changes in the levels of CA 19.9 went in line with the clinical course of the disease, but no apparent relationships were seen with the biological markers of angiogenesis. QoL and safety evaluations were comparable between treatment groups. Pharmacokinetic studies showed no influence of gemcitabine on the pharmacokinetic parameters of Cilengitide and vice versa.
There were no clinically important differences observed regarding efficacy, safety and QoL between the groups. The observations lay in the range of other clinical studies in this setting. The combination regimen was well tolerated with no adverse effects on the safety, tolerability and pharmacokinetics of either agent.