BMC Cancer (Dec 2006)

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

  • Katz Frieder,
  • Balcke Peter,
  • Hawkins Robert,
  • Scheithauer Werner,
  • Dobrowolski Frank,
  • Piedbois Pascal,
  • Herzog Peter,
  • Neyns Bart,
  • Stöger Herbert,
  • Hossfeld Dieter K,
  • Dittrich Christian,
  • Niedergethmann Marco,
  • Raedle Jochen,
  • Oettle Helmut,
  • Langrehr Jan M,
  • Friess Helmut,
  • Vermorken Jan,
  • van Belle Simon,
  • Davidson Neville,
  • Esteve Albert,
  • Castellano Daniel,
  • Kleeff Jörg,
  • Tempia-Caliera Adrien A,
  • Kovar Andreas,
  • Nippgen Johannes

DOI
https://doi.org/10.1186/1471-2407-6-285
Journal volume & issue
Vol. 6, no. 1
p. 285

Abstract

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Abstract Background 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. Methods 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. Results 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. Conclusion 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.