Annals of Oncology Advance Access published online on July 8, 2005
Annals of Oncology, doi:10.1093/annonc/mdi310
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1 Juravinski Cancer Centre, Hamilton, Ontario
* To whom correspondence should be addressed. Background: BAY 43-9006, an oral multi-kinase inhibitor, targets serine-threonine kinases and receptor tyrosine kinases, and affects the tumor and vasculature in preclinical models. Based on its pharmacologic effect, it may be a useful cancer treatment. This study determined the maximum tolerated dose (MTD) of BAY 43-9006 in 42 patients with advanced, refractory metastatic or recurrent solid tumors. Dose-limiting toxicities (DLTs), safety, pharmacokinetics and tumor response were also evaluated. Patients and methods: In this open-label, phase I, dose-escalation study, BAY 43-9006 was administered orally in repeated cycles of 35 days (28 days on/7 days off). Eight doses were investigated: from 50 mg every fourth day to 600 mg twice daily. Treatment continued until unacceptable toxicity, tumor progression or death. Results: The MTD was 400 mg twice daily. BAY 43-9006 was well tolerated, with mild to moderate toxicities; only six patients discontinued study therapy due to adverse events. DLTs consisted of hand-foot skin reaction in three of seven patients receiving 600 mg twice daily. Stable disease was achieved in 22% of patients; median duration of stable disease was 7.2 months. Consistent with its observed half-life of Conclusions: Results indicate that further clinical investigation of BAY 43-9006 is warranted, and suggest it could be a promising future therapy for patients with cancer.
Received December 23, 2004
Revised May 6, 2005
Accepted May 17, 2005
Original article
Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors
2 Princess Margaret Hospital, Toronto, Ontario
3 Bayer Inc., Toronto, Canada
4 Bayer Pharmaceuticals Corporation, West Haven, CT, USA
H. W. Hirte, E-mail: hal.hirte{at}hrcc.on.ca
Abstract 
27 h, BAY 43-9006 accumulated on multiple dosing. Increases in exposure were less than proportional to the increases in dose.
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