Sorafenib (BAY 43-9006)
A236 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).
Max E. Scheulen,1 Klaus Mross,2 Christian Dittrich,3 Andreas Hochhaus,4 Rudolf Morant,5 Dieter Kberle,6 Jrgen Krauss,1 Annette Frost,2 Christian Flashar,7 Lutz Edler,8 Iris Burkholter,8 Urban Scheuring,9 Brian Schwartz,10 Dirk Strumberg.7 Dept. Intern. Med. (Cancer Research),
West German Cancer Center,1 Essen, Germany, Tumor Biology Center at the University, 2 Freiburg, Germany, LBI-ACR VIEnna VIEnna, KFJ-Spital,3 Vienna, Austria, III. Dept.
Intern. Med., Hematol. & Oncol. Mannheim, Univ. of Heidelberg,4 Mannheim, Germany, Center for Tumordiagnosic and Prevention,5 St. Gallen, Switzerland, Kantonsspital,
6 St. Gallen, Switzerland, Dept. of Hematol. & Med. Oncol., Marienhospital Herne, Univ. of Bochum,7 Herne, Germany, German Cancer Research Center,8 Heidelberg, Germany, Bayer Vital GmbH,9 Leverkusen, Germany, Bayer Healthcare,10 West
Haven, CT.
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.
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 with no 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-TTP) of ³ 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-TTP from 10 to 30% in a one stage design.
Secondary endpoints were overall response, overall survival, toxicity according to Common Toxicity Criteria
(CTC v2.0) and drug safety. Results: A total of 47 pts with PC were enrolled between August 2004 and January 2005.
The majority of pts (n=30, 63.8%) were treated for
at least 6 weeks, and 4 pts were treated for > 33 weeks (33-39 wks).
Among the 36 pts evaluable for TTP,
9 pts (25%) showed stable disease ³ 12 weeks
and 27 pts (75%) showed disease progression:
15 pts with confirmed progressive disease
and 12 pts due to study withdrawal before 12 weeks among those 4 due to tumor-related death.
In the 36 pts (76.6%) evaluable for response,
a partial response lasting < 4 wks was
observed in one patient.
A total of 11 pts were not evaluable due to missing information (n=2) or study withdrawal before completing the first cycle (n=9).
There were 3 disease-related deaths in patients withdrawn from study.
All 47 pts are evaluable for toxicity and adverse events.
Serious adverse events were seen in 21 pts (44.7%) but
only one (2.1%) was determined to be drug-related.
Conclusion:
Preliminary results of this study indicate that sorafenib is active in PC. Further investigation in future trials |
