Annals of Oncology Advance Access originally published online on February 24, 2006
Annals of Oncology 2006 17(5):866-873; doi:10.1093/annonc/mdl017
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2006 European Society for Medical Oncology
Results of a Phase I trial of sorafenib (BAY 43-9006) in combination with doxorubicin in patients with refractory solid tumors
1 West German Cancer Center, University of Essen; 2 Department of Gastroenterology and Internal Medicine, Marienhospital Herne, University of Bochum; 3 Bayer HealthCare AG, Clinical Pharmacology, Wuppertal; 4 Bayer Pharmaceuticals Corporation, West Haven, CT, USA; 5 M.A.R.C.O. Institute for Clinical Research and Statistics – Dr. Wargenau, Düsseldorf; 6 Department of Hematology and Medical Oncology, Marienhospital Herne, University of Bochum, Germany
* Correspondence to: PD Dr. D. Strumberg, Department of Hematology and Medical Oncology, Marienhospital Herne, University of Bochum, Hölkeskampring 40, 44621 Herne, Germany. Email: dirk.strumberg{at}marienhospital-herne.de
Background: Sorafenib (BAY 43-9006), a novel, oral multi-kinase inhibitor, blocks serine/threonine and receptor tyrosine kinases in the tumor and vasculature. Sorafenib demonstrated single-agent activity in Phase I studies, and was tolerated and inhibited tumor growth in combination with doxorubicin in preclinical studies. This Phase I dose-escalation study determined the safety, pharmacokinetics and efficacy of sorafenib plus doxorubicin.
Patients and methods: Thirty-four patients with refractory, solid tumors received doxorubicin 60 mg/m2 on Day 1 of 3-week cycles, and oral sorafenib from Day 4 of Cycle 1 at 100, 200 or 400 mg bid.
Results: Common drug-related adverse events were neutropenia (56%), hand–foot skin reaction (44%), stomatitis (32%), and diarrhea (32%). The maximum tolerated dose was not reached. One patient with pleural mesothelioma achieved a partial response (modified WHO criteria) and remained on therapy for 39.7 weeks. Fifteen patients (48%) achieved stable disease for 
12 weeks. Doxorubicin exposure increased moderately with sorafenib 400 mg bid. The pharmacokinetics of sorafenib and doxorubicinol were not affected.
Conclusion: Sorafenib 400 mg bid plus doxorubicin 60 mg/m2 was well tolerated. The increased doxorubicin exposure with sorafenib 400 mg bid did not result in significantly increased toxicity; low patient numbers make the clinical significance of this unclear. These promising efficacy results justify further clinical investigation.
Key words: BAY 43-9006, doxorubicin, Phase I, Raf kinase, sorafenib
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. A. Tran, C. D. Smith, M. Kester, and G. P. Robertson Combining Nanoliposomal Ceramide with Sorafenib Synergistically Inhibits Melanoma and Breast Cancer Cell Survival to Decrease Tumor Development Clin. Cancer Res., June 1, 2008; 14(11): 3571 - 3581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Adjei, J. R. Molina, S. J. Mandrekar, R. Marks, J. R. Reid, G. Croghan, L. J. Hanson, J. R. Jett, C. Xia, C. Lathia, et al. Phase I Trial of Sorafenib in Combination with Gefitinib in Patients with Refractory or Recurrent Non Small Cell Lung Cancer Clin. Cancer Res., May 1, 2007; 13(9): 2684 - 2691. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Strumberg, J. W. Clark, A. Awada, M. J. Moore, H. Richly, A. Hendlisz, H. W. Hirte, J. P. Eder, H.-J. Lenz, and B. Schwartz Safety, Pharmacokinetics, and Preliminary Antitumor Activity of Sorafenib: A Review of Four Phase I Trials in Patients with Advanced Refractory Solid Tumors Oncologist, April 1, 2007; 12(4): 426 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Gridelli, P. Maione, F. Del Gaizo, G. Colantuoni, C. Guerriero, C. Ferrara, D. Nicolella, D. Comunale, A. De Vita, and A. Rossi Sorafenib and Sunitinib in the Treatment of Advanced Non-Small Cell Lung Cancer Oncologist, February 1, 2007; 12(2): 191 - 200. [Abstract] [Full Text] [PDF]
|
|