Tuesday, February 28th, 2006.

Annals of Oncology. Published online on February 24, 2006 [Link]

H. Richly ¹, B. F. Henning ², P. Kupsch ¹, K. Passarge ¹, M. Grubert ¹, R. A. Hilger ¹, O. Christensen ³, E. Brendel ³, B. Schwartz ⁴, M. Ludwig ⁵, C. Flashar ⁶, R. Voigtmann ⁶, M. E. Scheulen ¹, S. Seeber ¹, and D. Strumberg ^{1 *}

¹ West German Cancer Center, University of Essen, Germany

² Department of Gastroenterology and Internal Medicine, Marienhospital Herne, University of Bochum, Germany

³ Bayer HealthCare AG, Clinical Pharmacology, Wuppertal, Germany

⁴ Bayer Pharmaceuticals Corporation, West Haven, CT, USA

⁵ M.A.R.C.O. Institute for Clinical Research and Statistics - Dr. Wargenau, Düsseldorf, Germany

⁶ Department of Hematology and Medical Oncology, Marienhospital Herne, University of Bochum, Germany

^* To whom correspondence should be addressed: D. Strumberg, E-mail: dirk.strumberg@marienhospital-herne.de

Abstract

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.

Keywords: BAY 43-9006; doxorubicin; Phase I; Raf kinase; sorafenib.

Glossary

therapy

any of the measures taken to treat a disease. Unproven therapy is any therapy that has not been scientifically tested and approved. Use of an unproven therapy instead of standard (proven) therapy is called alternative therapy. Some alternative therapies have dangerous or even life-threatening side effects. For others, the main danger is that a patient may lose the opportunity to benefit from standard therapy. Complementary therapy, on the other hand, refers to therapies used in addition to standard therapy. Some complementary therapies may help relieve certain symptoms of cancer, relieve side effects of standard cancer therapy, or improve a patient's sense of well-being. The ACS recommends that patients considering use of any alternative or complementary therapy discuss this with their health care team.

stomatitis

(sto-ma-ti-tis) inflammation or ulcers of mouth area. Stomatitis can be a side effect of some kinds of chemotherapy.

oncology

(on-call-o-jee) the branch of medicine concerned with the diagnosis and treatment of cancer.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

tumor

an abnormal lump or mass of tissue. Tumors can be benign (not cancerous) or malignant (cancerous).

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

« Mesothelioma Line Main Page.