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Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid...
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| Zeitschriftentitel: | Journal of Clinical Oncology |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , |
| In: | Journal of Clinical Oncology, 23, 2005, 5, S. 965-972 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Clinical Oncology (ASCO)
|
| Schlagwörter: |
| author_facet |
Strumberg, Dirk Richly, Heike Hilger, Ralf A. Schleucher, Norbert Korfee, Sonke Tewes, Mitra Faghih, Markus Brendel, Erich Voliotis, Dimitris Haase, Claus G. Schwartz, Brian Awada, Ahmad Voigtmann, Rudolf Scheulen, Max E. Seeber, Siegfried Strumberg, Dirk Richly, Heike Hilger, Ralf A. Schleucher, Norbert Korfee, Sonke Tewes, Mitra Faghih, Markus Brendel, Erich Voliotis, Dimitris Haase, Claus G. Schwartz, Brian Awada, Ahmad Voigtmann, Rudolf Scheulen, Max E. Seeber, Siegfried |
|---|---|
| author |
Strumberg, Dirk Richly, Heike Hilger, Ralf A. Schleucher, Norbert Korfee, Sonke Tewes, Mitra Faghih, Markus Brendel, Erich Voliotis, Dimitris Haase, Claus G. Schwartz, Brian Awada, Ahmad Voigtmann, Rudolf Scheulen, Max E. Seeber, Siegfried |
| spellingShingle |
Strumberg, Dirk Richly, Heike Hilger, Ralf A. Schleucher, Norbert Korfee, Sonke Tewes, Mitra Faghih, Markus Brendel, Erich Voliotis, Dimitris Haase, Claus G. Schwartz, Brian Awada, Ahmad Voigtmann, Rudolf Scheulen, Max E. Seeber, Siegfried Journal of Clinical Oncology Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid Tumors Cancer Research Oncology |
| author_sort |
strumberg, dirk |
| spelling |
Strumberg, Dirk Richly, Heike Hilger, Ralf A. Schleucher, Norbert Korfee, Sonke Tewes, Mitra Faghih, Markus Brendel, Erich Voliotis, Dimitris Haase, Claus G. Schwartz, Brian Awada, Ahmad Voigtmann, Rudolf Scheulen, Max E. Seeber, Siegfried 0732-183X 1527-7755 American Society of Clinical Oncology (ASCO) Cancer Research Oncology http://dx.doi.org/10.1200/jco.2005.06.124 <jats:sec><jats:title>Purpose</jats:title><jats:p> BAY 43-9006 is a novel dual-action Raf kinase and vascular endothelial growth factor receptor inhibitor that inhibits tumor cell proliferation and angiogenesis. This study established the safety and pharmacokinetics of BAY 43-9006 in 69 patients with advanced refractory solid tumors. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> BAY 43-9006 (50 to 800 mg) was administered once or twice daily on a varying weekly schedule. Pharmacokinetic sampling was performed in all patients; preliminary tumor response was also assessed. The effect of BAY 43-9006 on phorbol myristate acetate–stimulated ERK phosphorylation in peripheral blood lymphocytes was studied using flow cytometry. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Mild to moderate diarrhea was the most common (55%) treatment-related adverse event. The maximum-tolerated dose was 400 mg bid continuous. Dose-limiting toxicities were grade 3 diarrhea and fatigue at 800 mg bid, and grade 3 skin toxicity at 600 mg bid. BAY 43-9006 pharmacokinetics were highly variable for single and multiple dosing, and toxicity did not appear to be dose dependent. Significant decreases of phorbol myristate acetate–stimulated ERK phosphorylation (P < .01) were identified at doses ≥ 200 mg bid continuous. Forty-five patients were assessable for efficacy; one patient had a partial response (hepatocellular carcinoma at 400 mg bid continuous), 25 patients had stable disease, with eight lasting > 6 months and five for >12 months. Eighteen patients had progressive disease, and tumor response could not be evaluated in one patient. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Oral BAY 43-9006 was well tolerated and appeared to provide some clinical benefits. Based on the results of this study, BAY 43-9006 at 400 mg bid continuous is recommended for ongoing and future studies. </jats:p></jats:sec> Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid Tumors Journal of Clinical Oncology |
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| title |
Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid Tumors |
| title_unstemmed |
Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid Tumors |
| title_full |
Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid Tumors |
| title_fullStr |
Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid Tumors |
| title_full_unstemmed |
Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid Tumors |
| title_short |
Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid Tumors |
| title_sort |
phase i clinical and pharmacokinetic study of the novel raf kinase and vascular endothelial growth factor receptor inhibitor bay 43-9006 in patients with advanced refractory solid tumors |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1200/jco.2005.06.124 |
| publishDate |
2005 |
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965-972 |
| description |
<jats:sec><jats:title>Purpose</jats:title><jats:p> BAY 43-9006 is a novel dual-action Raf kinase and vascular endothelial growth factor receptor inhibitor that inhibits tumor cell proliferation and angiogenesis. This study established the safety and pharmacokinetics of BAY 43-9006 in 69 patients with advanced refractory solid tumors. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> BAY 43-9006 (50 to 800 mg) was administered once or twice daily on a varying weekly schedule. Pharmacokinetic sampling was performed in all patients; preliminary tumor response was also assessed. The effect of BAY 43-9006 on phorbol myristate acetate–stimulated ERK phosphorylation in peripheral blood lymphocytes was studied using flow cytometry. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Mild to moderate diarrhea was the most common (55%) treatment-related adverse event. The maximum-tolerated dose was 400 mg bid continuous. Dose-limiting toxicities were grade 3 diarrhea and fatigue at 800 mg bid, and grade 3 skin toxicity at 600 mg bid. BAY 43-9006 pharmacokinetics were highly variable for single and multiple dosing, and toxicity did not appear to be dose dependent. Significant decreases of phorbol myristate acetate–stimulated ERK phosphorylation (P < .01) were identified at doses ≥ 200 mg bid continuous. Forty-five patients were assessable for efficacy; one patient had a partial response (hepatocellular carcinoma at 400 mg bid continuous), 25 patients had stable disease, with eight lasting > 6 months and five for >12 months. Eighteen patients had progressive disease, and tumor response could not be evaluated in one patient. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Oral BAY 43-9006 was well tolerated and appeared to provide some clinical benefits. Based on the results of this study, BAY 43-9006 at 400 mg bid continuous is recommended for ongoing and future studies. </jats:p></jats:sec> |
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| author | Strumberg, Dirk, Richly, Heike, Hilger, Ralf A., Schleucher, Norbert, Korfee, Sonke, Tewes, Mitra, Faghih, Markus, Brendel, Erich, Voliotis, Dimitris, Haase, Claus G., Schwartz, Brian, Awada, Ahmad, Voigtmann, Rudolf, Scheulen, Max E., Seeber, Siegfried |
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| description | <jats:sec><jats:title>Purpose</jats:title><jats:p> BAY 43-9006 is a novel dual-action Raf kinase and vascular endothelial growth factor receptor inhibitor that inhibits tumor cell proliferation and angiogenesis. This study established the safety and pharmacokinetics of BAY 43-9006 in 69 patients with advanced refractory solid tumors. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> BAY 43-9006 (50 to 800 mg) was administered once or twice daily on a varying weekly schedule. Pharmacokinetic sampling was performed in all patients; preliminary tumor response was also assessed. The effect of BAY 43-9006 on phorbol myristate acetate–stimulated ERK phosphorylation in peripheral blood lymphocytes was studied using flow cytometry. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Mild to moderate diarrhea was the most common (55%) treatment-related adverse event. The maximum-tolerated dose was 400 mg bid continuous. Dose-limiting toxicities were grade 3 diarrhea and fatigue at 800 mg bid, and grade 3 skin toxicity at 600 mg bid. BAY 43-9006 pharmacokinetics were highly variable for single and multiple dosing, and toxicity did not appear to be dose dependent. Significant decreases of phorbol myristate acetate–stimulated ERK phosphorylation (P < .01) were identified at doses ≥ 200 mg bid continuous. Forty-five patients were assessable for efficacy; one patient had a partial response (hepatocellular carcinoma at 400 mg bid continuous), 25 patients had stable disease, with eight lasting > 6 months and five for >12 months. Eighteen patients had progressive disease, and tumor response could not be evaluated in one patient. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Oral BAY 43-9006 was well tolerated and appeared to provide some clinical benefits. Based on the results of this study, BAY 43-9006 at 400 mg bid continuous is recommended for ongoing and future studies. </jats:p></jats:sec> |
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| spelling | Strumberg, Dirk Richly, Heike Hilger, Ralf A. Schleucher, Norbert Korfee, Sonke Tewes, Mitra Faghih, Markus Brendel, Erich Voliotis, Dimitris Haase, Claus G. Schwartz, Brian Awada, Ahmad Voigtmann, Rudolf Scheulen, Max E. Seeber, Siegfried 0732-183X 1527-7755 American Society of Clinical Oncology (ASCO) Cancer Research Oncology http://dx.doi.org/10.1200/jco.2005.06.124 <jats:sec><jats:title>Purpose</jats:title><jats:p> BAY 43-9006 is a novel dual-action Raf kinase and vascular endothelial growth factor receptor inhibitor that inhibits tumor cell proliferation and angiogenesis. This study established the safety and pharmacokinetics of BAY 43-9006 in 69 patients with advanced refractory solid tumors. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> BAY 43-9006 (50 to 800 mg) was administered once or twice daily on a varying weekly schedule. Pharmacokinetic sampling was performed in all patients; preliminary tumor response was also assessed. The effect of BAY 43-9006 on phorbol myristate acetate–stimulated ERK phosphorylation in peripheral blood lymphocytes was studied using flow cytometry. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Mild to moderate diarrhea was the most common (55%) treatment-related adverse event. The maximum-tolerated dose was 400 mg bid continuous. Dose-limiting toxicities were grade 3 diarrhea and fatigue at 800 mg bid, and grade 3 skin toxicity at 600 mg bid. BAY 43-9006 pharmacokinetics were highly variable for single and multiple dosing, and toxicity did not appear to be dose dependent. Significant decreases of phorbol myristate acetate–stimulated ERK phosphorylation (P < .01) were identified at doses ≥ 200 mg bid continuous. Forty-five patients were assessable for efficacy; one patient had a partial response (hepatocellular carcinoma at 400 mg bid continuous), 25 patients had stable disease, with eight lasting > 6 months and five for >12 months. Eighteen patients had progressive disease, and tumor response could not be evaluated in one patient. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Oral BAY 43-9006 was well tolerated and appeared to provide some clinical benefits. Based on the results of this study, BAY 43-9006 at 400 mg bid continuous is recommended for ongoing and future studies. </jats:p></jats:sec> Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid Tumors Journal of Clinical Oncology |
| spellingShingle | Strumberg, Dirk, Richly, Heike, Hilger, Ralf A., Schleucher, Norbert, Korfee, Sonke, Tewes, Mitra, Faghih, Markus, Brendel, Erich, Voliotis, Dimitris, Haase, Claus G., Schwartz, Brian, Awada, Ahmad, Voigtmann, Rudolf, Scheulen, Max E., Seeber, Siegfried, Journal of Clinical Oncology, Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid Tumors, Cancer Research, Oncology |
| title | Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid Tumors |
| title_full | Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid Tumors |
| title_fullStr | Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid Tumors |
| title_full_unstemmed | Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid Tumors |
| title_short | Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid Tumors |
| title_sort | phase i clinical and pharmacokinetic study of the novel raf kinase and vascular endothelial growth factor receptor inhibitor bay 43-9006 in patients with advanced refractory solid tumors |
| title_unstemmed | Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid Tumors |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1200/jco.2005.06.124 |