| SORAFENIB (BAY 43-9006) SIDE EFFECTS |
The Food and Drug Administration (FDA) approved Nexavar (sorafenib tosylate), a new anti-
cancer medicine used to treat adults with advanced renal cell carcinoma, the most common
type of kidney cancer.
"The approval of Nexavar to treat advanced kidney cancer brings a much needed option for
this group of cancer patients," said Dr. Steven Galson, Director of FDA's Center for Drug
Evaluation and Research (CDER). "FDA is working hard to support the development of new
and effective treatments for patients with cancer and other serious illnesses who have limited
alternatives."
In the United States, kidney cancer accounts for approximately 3 percent of all adult cancers.
According to the American Cancer Society, about 32,000 new cases are diagnosed and
about 12,000 people die from the disease annually. Kidney cancer occurs most often in
people between the ages of 50 and 70, affects men almost twice as often as women and, if
detected early enough, may be curable surgically. However, tumors that are advanced (i.e.,
cannot be surgically removed or have spread to other parts of the body) are difficult to treat.
Two studies in patients with advanced kidney cancer have shown that patients treated with
Nexavar had more time before tumor progression or death. In the larger study, most patients
had previously received treatment with interleukin-2 or interferon. The median time to tumor
progression or death in the Nexavar treated arm was 167 days compared to 84 days in
people not treated with the drug.
Some common temporary side effects reported with Nexavar are rash, diarrhea, increases in
blood pressure, and redness, pain swelling, or blisters on the palms of the hands or soles of
the feet.
Nexavar will be distributed and marketed by Bayer Pharmaceuticals Corporation of
Westhaven, CT.
Development of Nexavar (sorafenib tosylate)
In pre-clinical models, sorafenib targeted members of two classes of kinases involved in both
tumor cell proliferation (tumor growth; An increase in the number of cells as a result of cell
growth and cell division.) and tumor angiogenesis (tumor blood supply; The formation of new
blood vessels). The kinases included RAF kinase, VEGFR-2, VEGFR-3, PDGFR-;, KIT, FLT-
3 and RET. [1]
Currently, Bayer and Onyx are conducting large, international, multicenter Phase III clinical
studies of sorafenib (BAY 43-9006) in patients with advanced kidney cancer, advanced
primary liver cancer and metastatic melanoma. Because Sorafenib (BAY 43-9006) is able to
inhibit multiple kinases, this agent is also being evaluated in single-agent Phase II clinical
trials in lung, breast, and other cancers, along with several Phase I/II clinical trials studying the
agent in combination with a range of standard chemotherapeutics and other anticancer
agents (such as carboplatin/paclitaxel, 5-Fu, docetaxel, capecitabine, oxaliplatin, irinotecan,
Gemcitabine, gefitinib, doxorubicin, DTIC and IFN. [2]
In May 2005, Bayer and Onyx reported at the annual meeting of the American Society of
Clinical Oncology that sorafenib was well tolerated and significantly delayed disease
progression in an ongoing Phase III clinical trial in patients with advanced kidney cancer. As
assessed by independent radiologic review, progression-free survival was doubled to a
median value of 24 weeks in patients receiving sorafenib, compared to 12 weeks for patients
receiving placebo. [2]
In July 2005, Bayer and Onyx submitted a New Drug Application (NDA) for possible approval
in this indication by the U.S. FDA. Subsequently, the NDA application had been accepted
and granted priority review status by the FDA. In September 2005, a Marketing Authorization
Application was submitted to the European Medicines Agency for approval to market
sorafenib within the European Union for the same indication. [2]
SORAFENIB SIDE EFFECTS
In a few studies, Sorafenib (BAY 43-9006) appeared to be safe, well-tolerated and showed
anti-tumor activities. The toxic effects of Sorafenib (BAY 43-9006) were manageable and
included hypertension, edema, diarrhea, hand and foot syndrome, rash, and hair loss where
the rash involved the scalp. [7]
In a Phase I study, 44 patients with advanced, refractory solid tumors were administered with
50 to 800 mg b.i.d of Sorafenib (BAY 43-9006) for repeated cycles of 21 days on/7 days off.
The side effects or the most frequently reported adverse events in this study were
gastrointestinal (75%), dermatologic (71%), constitutional (68%), pain (64%), or hepatic
(61%) related. Sorafenib (BAY 43-9006) was absorbed rapidly; steady-state conditions were
reached within 7 days. [5]
In another study, 69 patients with advanced refractory solid tumors were administered with 50
to 800 mg b.i.d of Sorafenib (BAY 43-9006). They found that mild to moderate diarrhea was
the most common (55%) treatment-related side effect. 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. [6]
PARTNERSHIP
According to Oxnyx online publication, Onyx is funding 50 percent of the development costs
for sorafenib. In return, Oxnyx has a 50/50 profit share in the United States, where they can
copromote the product with Bayer. Everywhere in the world except Japan, Oxynx share is
somewhat less than 50 percent since Bayer has exclusive marketing rights. In Japan, Bayer
funds product development, and Onyx will get a royalty based on any sales there.
ABOUT RAS AND RAF
Mitogen-activated protein kinase (MAPK) signaling pathway is important in transmitting
proliferative signals generated by cell surface receptors and cytoplasmic signaling elements
to the nucleus. Several important signaling elements of the MAPK pathway, particularly Ras
and Raf, are encoded by oncogenes, and as such, their structures and functions can be
modified, rendering them constitutively active.
Raf, which is an essential serine/threonine kinase constituent of the MAPK pathway and a
downstream effector of the central signal transduction mediator Ras, is activated in a wide
range of human malignancies by aberrant signaling upstream of the protein and activating
mutations of the protein itself, both of which confer a proliferative advantage.
Because the MAPK pathway is dys-regulated in a notable proportion of human malignancies,
many of its aberrant and critical components represent strategic targets for therapeutic
development against cancer. [3]
ABOUT VEGF AND EGF
Hypoxia-regulated genes such as vascular endothelial growth factor (VEGF) and epidermal
growth factor (EGF) are both important for tumor progression in renal cell carcinoma (RCC).
Results from a Phase III clinical trial with sorafenib show only a 2% response rate; however, a
statistically significant improvement in progression-free survival was observed. [4]
REFERENCE
[1] Bayer and Onyx Announce Access to Sorafenib (BAY 43-9006) for Individuals with
Advanced Renal Cell Carcinoma, Bayer HealthCare Press Release, May 14 2005.
[2] Products in the clinic – Sorafenib, Onyx Pharmaceuticals Online Publication, October 09.
2005.
[3] Beeram M et al, Raf: a strategic target for therapeutic development against cancer. J Clin
Oncol. 2005 Sep 20;23(27):6771-90. [4] Favaro JP and George DJ Targeted therapy in renal
cell carcinoma. Expert Opin Investig Drugs. 2005 Oct;14(10):1251-8. [5] Awada A et al,
Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7 days off
in patients with advanced, refractory solid tumours. Br J Cancer. 2005 May 23;92(10):1855-
61. [6] Strumberg D et al, 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. J Clin Oncol. 2005 Feb 10;23(5):965-72. Epub 2004 Dec
21. [7] Ahmad T and Eisen T Kinase inhibition with BAY 43-9006 in renal cell carcinoma. Clin
Cancer Res. 2004 Sep 15;10(18 Pt 2):6388S-92S.
cancer medicine used to treat adults with advanced renal cell carcinoma, the most common
type of kidney cancer.
"The approval of Nexavar to treat advanced kidney cancer brings a much needed option for
this group of cancer patients," said Dr. Steven Galson, Director of FDA's Center for Drug
Evaluation and Research (CDER). "FDA is working hard to support the development of new
and effective treatments for patients with cancer and other serious illnesses who have limited
alternatives."
In the United States, kidney cancer accounts for approximately 3 percent of all adult cancers.
According to the American Cancer Society, about 32,000 new cases are diagnosed and
about 12,000 people die from the disease annually. Kidney cancer occurs most often in
people between the ages of 50 and 70, affects men almost twice as often as women and, if
detected early enough, may be curable surgically. However, tumors that are advanced (i.e.,
cannot be surgically removed or have spread to other parts of the body) are difficult to treat.
Two studies in patients with advanced kidney cancer have shown that patients treated with
Nexavar had more time before tumor progression or death. In the larger study, most patients
had previously received treatment with interleukin-2 or interferon. The median time to tumor
progression or death in the Nexavar treated arm was 167 days compared to 84 days in
people not treated with the drug.
Some common temporary side effects reported with Nexavar are rash, diarrhea, increases in
blood pressure, and redness, pain swelling, or blisters on the palms of the hands or soles of
the feet.
Nexavar will be distributed and marketed by Bayer Pharmaceuticals Corporation of
Westhaven, CT.
Development of Nexavar (sorafenib tosylate)
In pre-clinical models, sorafenib targeted members of two classes of kinases involved in both
tumor cell proliferation (tumor growth; An increase in the number of cells as a result of cell
growth and cell division.) and tumor angiogenesis (tumor blood supply; The formation of new
blood vessels). The kinases included RAF kinase, VEGFR-2, VEGFR-3, PDGFR-;, KIT, FLT-
3 and RET. [1]
Currently, Bayer and Onyx are conducting large, international, multicenter Phase III clinical
studies of sorafenib (BAY 43-9006) in patients with advanced kidney cancer, advanced
primary liver cancer and metastatic melanoma. Because Sorafenib (BAY 43-9006) is able to
inhibit multiple kinases, this agent is also being evaluated in single-agent Phase II clinical
trials in lung, breast, and other cancers, along with several Phase I/II clinical trials studying the
agent in combination with a range of standard chemotherapeutics and other anticancer
agents (such as carboplatin/paclitaxel, 5-Fu, docetaxel, capecitabine, oxaliplatin, irinotecan,
Gemcitabine, gefitinib, doxorubicin, DTIC and IFN. [2]
In May 2005, Bayer and Onyx reported at the annual meeting of the American Society of
Clinical Oncology that sorafenib was well tolerated and significantly delayed disease
progression in an ongoing Phase III clinical trial in patients with advanced kidney cancer. As
assessed by independent radiologic review, progression-free survival was doubled to a
median value of 24 weeks in patients receiving sorafenib, compared to 12 weeks for patients
receiving placebo. [2]
In July 2005, Bayer and Onyx submitted a New Drug Application (NDA) for possible approval
in this indication by the U.S. FDA. Subsequently, the NDA application had been accepted
and granted priority review status by the FDA. In September 2005, a Marketing Authorization
Application was submitted to the European Medicines Agency for approval to market
sorafenib within the European Union for the same indication. [2]
SORAFENIB SIDE EFFECTS
In a few studies, Sorafenib (BAY 43-9006) appeared to be safe, well-tolerated and showed
anti-tumor activities. The toxic effects of Sorafenib (BAY 43-9006) were manageable and
included hypertension, edema, diarrhea, hand and foot syndrome, rash, and hair loss where
the rash involved the scalp. [7]
In a Phase I study, 44 patients with advanced, refractory solid tumors were administered with
50 to 800 mg b.i.d of Sorafenib (BAY 43-9006) for repeated cycles of 21 days on/7 days off.
The side effects or the most frequently reported adverse events in this study were
gastrointestinal (75%), dermatologic (71%), constitutional (68%), pain (64%), or hepatic
(61%) related. Sorafenib (BAY 43-9006) was absorbed rapidly; steady-state conditions were
reached within 7 days. [5]
In another study, 69 patients with advanced refractory solid tumors were administered with 50
to 800 mg b.i.d of Sorafenib (BAY 43-9006). They found that mild to moderate diarrhea was
the most common (55%) treatment-related side effect. 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. [6]
PARTNERSHIP
According to Oxnyx online publication, Onyx is funding 50 percent of the development costs
for sorafenib. In return, Oxnyx has a 50/50 profit share in the United States, where they can
copromote the product with Bayer. Everywhere in the world except Japan, Oxynx share is
somewhat less than 50 percent since Bayer has exclusive marketing rights. In Japan, Bayer
funds product development, and Onyx will get a royalty based on any sales there.
ABOUT RAS AND RAF
Mitogen-activated protein kinase (MAPK) signaling pathway is important in transmitting
proliferative signals generated by cell surface receptors and cytoplasmic signaling elements
to the nucleus. Several important signaling elements of the MAPK pathway, particularly Ras
and Raf, are encoded by oncogenes, and as such, their structures and functions can be
modified, rendering them constitutively active.
Raf, which is an essential serine/threonine kinase constituent of the MAPK pathway and a
downstream effector of the central signal transduction mediator Ras, is activated in a wide
range of human malignancies by aberrant signaling upstream of the protein and activating
mutations of the protein itself, both of which confer a proliferative advantage.
Because the MAPK pathway is dys-regulated in a notable proportion of human malignancies,
many of its aberrant and critical components represent strategic targets for therapeutic
development against cancer. [3]
ABOUT VEGF AND EGF
Hypoxia-regulated genes such as vascular endothelial growth factor (VEGF) and epidermal
growth factor (EGF) are both important for tumor progression in renal cell carcinoma (RCC).
Results from a Phase III clinical trial with sorafenib show only a 2% response rate; however, a
statistically significant improvement in progression-free survival was observed. [4]
REFERENCE
[1] Bayer and Onyx Announce Access to Sorafenib (BAY 43-9006) for Individuals with
Advanced Renal Cell Carcinoma, Bayer HealthCare Press Release, May 14 2005.
[2] Products in the clinic – Sorafenib, Onyx Pharmaceuticals Online Publication, October 09.
2005.
[3] Beeram M et al, Raf: a strategic target for therapeutic development against cancer. J Clin
Oncol. 2005 Sep 20;23(27):6771-90. [4] Favaro JP and George DJ Targeted therapy in renal
cell carcinoma. Expert Opin Investig Drugs. 2005 Oct;14(10):1251-8. [5] Awada A et al,
Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7 days off
in patients with advanced, refractory solid tumours. Br J Cancer. 2005 May 23;92(10):1855-
61. [6] Strumberg D et al, 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. J Clin Oncol. 2005 Feb 10;23(5):965-72. Epub 2004 Dec
21. [7] Ahmad T and Eisen T Kinase inhibition with BAY 43-9006 in renal cell carcinoma. Clin
Cancer Res. 2004 Sep 15;10(18 Pt 2):6388S-92S.
| FDA approved Nexavar (sorafenib toxylate) to treat adults with advanced renal cell carcinoma, the most common type of kidney cancer on December 20, 2005. Sorafenib (BAY 43-9006) is an oral multi-kinase inhibitor targeting serine/threonine and receptor tyrosine kinases in both the tumor cell and tumor vasculature. |
 |  |  |  |  |
THIS WEBSITE TALKS ABOUT THE SIDE EFFECTS AND THE POTENTIAL HEALTH BENEFITS OF HERBS, SUPPLEMENTS,
PHYTONUTRIENTS AND DRUG PRODUCTS. THIS WEBSITE ALSO TALKS ABOUT SOME POPULAR HEALTH ISSUES AND DISEASES.
ARTICLES IN THIS WEB SITE IS FOR YOUR REFERENCE ONLY. IF YOU HAVE ANY QUESTION, YOU SHOULD CONSULT WITH YOUR
DOCTOR IMMEDIATELY. ALL RIGHTS RESERVED. DO NOT COPY NOR TRANSFER ARTICLES TO OTHER WEBSITES NOR OTHER FORMS
OF PUBLICATIONS. Privacy Policy. ARTICLE INDEX
PHYTONUTRIENTS AND DRUG PRODUCTS. THIS WEBSITE ALSO TALKS ABOUT SOME POPULAR HEALTH ISSUES AND DISEASES.
ARTICLES IN THIS WEB SITE IS FOR YOUR REFERENCE ONLY. IF YOU HAVE ANY QUESTION, YOU SHOULD CONSULT WITH YOUR
DOCTOR IMMEDIATELY. ALL RIGHTS RESERVED. DO NOT COPY NOR TRANSFER ARTICLES TO OTHER WEBSITES NOR OTHER FORMS
OF PUBLICATIONS. Privacy Policy. ARTICLE INDEX
 | |  | |  | |  | |  | |  |