gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

Phase II Study of First Line Sorafenib (BAY 43-9006) in Patients with Locally Advanced and/or Metastatic Pancreatic Cancer – a Study of the Central European Society for Anticancer Drug Research - EWIV (CESAR)

Meeting Abstract

  • corresponding author presenting/speaker Max E. Scheulen - Central European Society for Anticancer Drug Research - EWIV, Wien, Österreich , Essen, Deutschland
  • Klaus Mross - Klinik für Tumorbiologie, Freiburg
  • Christian Dittrich - LBI-ACR VIEnna und ACR-ITR VIEnna, Kaiser Franz Josef-Spital, Österreich
  • Andreas Hochhaus - III. Medizinische Klinik, Universitätsklinikum Mannheim, Universität Heidelberg
  • Rudolf Morant - Zentrum für Tumordiagnostik und Prävention, St. Gallen, Schweiz
  • Dieter Köberle - Abteilung Medizinische Onkologie, Kantonsspital, St. Gallen, Schweiz
  • Jürgen Krauß - Innere Klinik und Poliklinik (Tumorforschung), Universitätsklinikum Essen
  • Annette Frost - Klinik für Tumorbiologie, Freiburg
  • Christian Flashar - Abteilung für Hämatologie und Onkologie, Marienhospital Herne, Ruhruniversität Bochum
  • Lutz Edler - Deutsches Krebsforschungszentrum Heidelberg
  • Urban Scheuring - Bayer Vital GmbH, Leverkusen
  • Dirk Strumberg - Abteilung für Hämatologie und Onkologie, Marienhospital Herne, Ruhruniversität Bochum

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO127

The electronic version of this article is the complete one and can be found online at:

Published: March 20, 2006

© 2006 Scheulen et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Background: Sorafenib (BAY 43-9006) is a novel orally active multi-kinase inhibitor with anti-angiogenic and anti-proliferative activity by blocking both the Raf/MEK/ERK pathway at the level of Raf kinase and the receptor tyrosine kinases VEGFR-2 and PDGFR-ß. Previous single-agent phase I studies showed that sorafenib is well tolerated, with manageable and reversible side effects, most commonly hand-foot skin (HFS) reaction, rash, fatigue, and diarrhea. This phase II study was conducted to investigate the activity of sorafenib in previously untreated patients (pts) with locally advanced and/or metastatic pancreatic cancer (PC).

Methods: Pts received sorafenib 400 mg bid by continuous oral dosing. Pts without prior systemic therapy for advanced disease and at least one uni-dimensional measurable lesion according to the RECIST-criteria were eligible for study entry. The primary objective was the proportion of evaluable patients with time to progression (PP-TTP12) of ≥ 12 weeks. A minimum of 37 evaluable pts (those completing at least 4 weeks [one cycle] of sorafenib therapy) were required to detect an increase in PP-TTP12 from 10 to 30% in a one stage design. Secondary endpoints were overall response, overall survival, toxicity according to Common Toxicity Criteria (CTC v3.0) and drug safety.

Results: A total of 47 pts with PC was enrolled between August 2004 and January 2005. One pt had to be excluded because of lack of a target lesion. The PP-TTP12 in the full analysis set of 46 pts was 26.1% (12 pts, 95%CI 14.3-41.1%) with one PR (not-confirmed) and 11 SD until 12 weeks. The null hypothesis PP-TTP12 ≤ 10% was rejected in a one-sided binominal test with p = 0.0015. Thus, this phase II trial concludes a significant effect and demonstrates efficacy with respect to the primary objective. Median TTP was 6.3 wks (5.9-11.9 wks) with a 12-week rate of 30.1% (18.8-48.2%) and median survival was 21.7 wks (14.6-39.3 wks). All 47 pts are evaluable for toxicity and adverse events (AE). There were 19 grade 3&4 AE including two with definite relation to treatment (one hand-foot syndrome, one diarrhea).

Conclusion: Sorafenib demonstrates activity with respect to PP-TTP12 in pts with PC and has only mild toxicity on long-term continuous oral administration. Thus, further investigations in future trials are necessary.