Nexavar
From Kidney Cancer Resource
Overview
To view the Bayer Pharmaceuticals Corporation web-site Click Here
To view Bayer's web site for Nexavar Click Here
Bayer the manufacturer of Sorafenib interchange the name with Nexavar in the public domain for marketing.
EUROPEAN PUBLIC ASSESSMENT REPORT - NEXAVAR
- Summary for the public
Sorafenib (rINN), marketed as Nexavar by Bayer, is a drug approved for the treatment of advanced renal cell cancer. It is a small molecular inhibitor of Raf kinase, PDGF (platelet-derived growth factor) ,VEGF receptor 2 & 3 kinases and c Kit the receptor for Stem cell factor. A growing number of drugs target most of these pathways. The originality [1] of Sorafenib lays in its simultaneous targeting of the Raf/Mek/Erk pathway.
Used in the treatment of patients with advanced Renal Cell Cancer when standard therapy has not helped to stop the disease or is considered unsuitable.
Trials have shown that sorafenib can make the cancer stop growing for longer than people taking a placebo. It has also been found to slow the growth of advanced Kidney Cancer.
The European Commission approved the use of sorafenib for advanced Renal Cell Cancer|renal cell cancer in 2006.
About Nexavar
Nexavar targets both the tumor cell and tumor vasculature. In preclinical studies, Nexavar has been shown to target members of two classes of kinases known to be involved in both cell proliferation (growth) and angiogenesis (blood supply) - two important processes that enable cancer growth. These kinases included Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET. Preclinical models have also demonstrated that Raf/MEK/ERK has a role in HCC; therefore blocking signaling through Raf-1 may offer therapeutic benefits in HCC.
Nexavar is currently approved in more than 30 countries for liver cancer and in more than 60 countries for the treatment of patients with advanced kidney cancer. Nexavar is also being evaluated by the companies, international study groups, government agencies and individual investigators as a single agent or combination treatment in a wide range of other cancers, including non-small cell lung cancer (NSCLC), metastatic melanoma, breast cancer and as an adjuvant therapy for kidney cancer and liver cancer.
Important Safety Considerations For Patients Taking Nexavar
Based on the currently approved U.S. package insert for the treatment of patients with unresectable hepatocellular carcinoma, hypertension may occur early in the course of therapy and blood pressure should be monitored weekly during the first six weeks of therapy and treated as needed.
Bleeding with a fatal outcome from any site was reported in 2.4% for Nexavar and 4% in placebo. The incidence of treatment-emergent cardiac ischemia/infarction was 2.7% for Nexavar vs. 1.3% for placebo.
Most common adverse events reported with Nexavar in patients with unresectable HCC were diarrhea, fatigue, abdominal pain, weight loss, anorexia, nausea and hand-foot skin reaction. Grade 3/4 adverse events were 45% for Nexavar vs. 32% for placebo. Women of child-bearing potential should be advised to avoid becoming pregnant and advised against breast-feeding.
In cases of any severe or persistent side effects, temporary treatment interruption, dose modification or permanent discontinuation should be considered. For information about Nexavar including U.S. Nexavar prescribing information, visit http://www.nexavar.com/ or call 1.866.NEXAVAR (1.866.639.2827).
Status world wide
Sorafenib is currently approved in over 70 countries for the treatment of patients with advanced kidney cancer. Jul-2008
Status in the US
Sorafenib was approved by the U.S. Food and Drug Administration (FDA) on December 20, 2005 and received a E.U. marketing authorisation on July 19, 2006
Status in Malasia
“Sorafenib was approved and launched in Malaysia for the treatment of kidney cancer in Aug-2007”
Status in the UK
As of June 2007 this has not yet been approved by N.I.C.E (National Institute for Clinical Excellence). Each PCT (Primary Care Trust) currently has to make its own judgment call based on the facts of each case.
There is an Early Day Motion lodged in the House of Commons by an MP regarding Nexavar
Further General Data
NetDoctor on Nexavar
- Broad Overview Data of Nexavar
Articles
HEATON-HARRIS, Chris 26-Aug-08
- PRESS RELEASE - Chris HEATON-HARRIS MEP continued support....
DAVIES, David (KC) 26-Aug-08
- PRESS RELEASE - David T.C. DAVIES MP (Monmouthshire) continued support....
Yours Magazine (KC) 26-Aug-08
- The Living Nightmare 'I'm not ready to die'....
BBC (KC) 26-Aug-08
The Times (KC) 26-Aug-08
James Whale Press Release 25-Aug-08
- James Whale Press Release....
Echo (KC) 26-Aug-08
- Backlash over axe for specialist drugs cash....
Oxford Mail (KC) 26-Aug-08
- Doctors back cancer drug protest....
Renal & Urology News (KC) 25-Aug-08
- Difficult RCC Cases Respond to New Drug....
Telegraph (KC) 25-Aug-08
- Senior doctor accuses Government of destroying NHS....
The Guardian (KC) 25-Aug-08
- Specialists question decision not to fund drugs for kidney cancer....
LINDER MYERS SOLICITORS 24-Aug-08 Press Release
- Kidney Cancer Jean Murphy - press release....
BBC (KC) 24-Aug-08
- Experts in drug 'ration' warning....
Sunday Times (KC) 24-Aug-08
- Cancer drugs due a review....
BBC (KC) 24-Aug-08
- Experts in drug 'ration' warning
MedicExchange (KC) 22-Aug-08
- Sorafenib and bevacizumab promising for solid tumors
Daily Mail (KC) 12-Aug-08
Belfast Telegraph (KC) 12-Aug-08
- NHS should not save lives if it costs too much: watchdog
MedicalNewsToday (KC) 10-Aug-08
The Times (KC) 08-Aug-08
Swansea Evening Post (KC) 08-Aug-08
- 'HOW CAN THEY PUT A PRICE ON LIFE?'
The Times (KC) 07-Aug-08 / 01
- Case Study: ‘After three tablets, my tumour shrank’
Bristol Evening Post (KC) 07-Aug-08
- NHS advised not to fund kidney cancer drugs
The Times (KC) 07-Aug-08
- £35,000-a-year kidney cancer drugs too costly for NHS
BBC (KC) 07-Aug-08
Daily Mail KC 07-Aug-08-02
- Nasty truth about NICE: It's the body that rations NHS drugs. But this leading cancer specialist says its decisions are deeply flawed
Daily Mail (KC) 07-Aug-08
The Sun (KC) 07-Aug-08
- 4 kidney cancer drugs are axed
The Star (KC) 13-Jul-08
- Bayer Schering Pharma’s oral anti-cancer drug sorafenib has been approved in Malaysia for the treatment of liver cancer.
Cancer Consultants (KC) 07-Feb-08
- Blood Pressure Monitoring Recommended for Kidney Cancer Patients Treated with Nexavar®
USNews (KC) 22-Jan-08
- Liver Cancer Drug Raises Blood Pressure Patients taking Nexavar need to be monitored closely, study says....
EURO2day (KC) 22-Jan-08
- Bayer says Nexavar risks highlighted by Lancet are reflected in current label
2006.Nov-Dec. - Details from Pub Meds
1: Urol Oncol. 2006 Nov-Dec;24(6):560.
Phase II placebo-controlled randomized discontinuation Trial|trial]] of sorafenib in patients with metastatic renal cell carcinoma Ratain MJ, Eisen T. Stadler WM, Flaherty KT, Kaye SB, Rosner GL, Gore M, Desai A, Patnaik A, Xiong HQ, Rowinsky E, Abbruzzese JL, Xia C, Simantov R, Schwartz B. O'Dwyer PJ, University of Chicago, Chicago, IL.Russo P.
PURPOSE: This phase II randomized discontinuation trial evaluated the effects of sorafenib (BAY 43-9006), an oral multikinase inhibitor targeting the tumor and vasculature, on tumor growth in patients with metastatic renal cell carcinoma.
PATIENTS AND METHODS: Patients initially received oral sorafenib 400 mg twice daily during the initial run-in period. After 12 weeks, patients with changes in bidimensional tumor measurements that were less than 25% from baseline were randomly assigned to sorafenib or placebo for an additional 12 weeks; patients with >/=25% tumor shrinkage continued open-label sorafenib; patients with >/=25% tumor growth discontinued treatment. The primary end point was the percentage of randomly assigned patients remaining progression free at 24 weeks after the initiation of sorafenib.
RESULTS: Of 202 patients treated during the run-in period, 73 patients had tumor shrinkage of >/=25%. Sixty-five patients with stable disease at 12 weeks were randomly assigned to sorafenib (n = 32) or placebo (n = 33). At 24 weeks, 50% of the sorafenib-treated patients were progression free versus 18% of the placebo-treated patients (P = .0077). Median progression-free survival (PFS) from randomization was significantly longer with sorafenib (24 weeks) than placebo (6 weeks; P = .0087).
Median overall PFS was 29 weeks for the entire renal cell carcinoma population (n = 202). Sorafenib was readministered in 28 patients whose disease progressed on placebo; these patients continued on sorafenib until further progression, for a median of 24 weeks. Common adverse events were skin rash/desquamation, hand-foot skin reaction, and fatigue; 9% of patients discontinued therapy, and no patients died from toxicity.
CONCLUSION: Sorafenib has significant disease-stabilizing activity in metastatic renal cell carcinoma and is tolerable with chronic daily therapy.
PMID: 17138147 [PubMed - in process]
To see the original of this article Click Here
Anyone with experience of using/taking Sorafenib or knows of UK Trials, usage, availability and efficacy can they please post their experiences as a new Comment in this section.
21-Sep-2007 - Evolving role of novel targeted agents in renal cell carcinoma.
Oncology (Williston Park). 2007 Sep ;21 (10):1175-80; discussion 1184, 1187, 1190 17926797 Evolving role of novel targeted agents in renal cell carcinoma. [My paper] Thomas E Hutson , Robert A Figlin The treatment of metastatic renal cell carcinoma (RCC) has changed dramatically over the past few years. An improved understanding of the biology of RCC has resulted in the development of novel targeted therapeutic agents that have altered the natural history of this disease.
In particular, the hypoxia-inducible factor (HIF)/vascular endothelial growth factor (VEGF) pathway and the mammalian target of rapamycin (mTOR) signal transduction pathway have been exploited. Sunitinib malate (Sutent), sorafenib tosylate (Nexavar), bevacizumab (Avastin)/interferon alfa, and temsirolimus (Torisel) have improved clinical outcomes in randomized trials by inhibiting these tumorigenic pathways.
Combinations and sequences of these agents are being evaluated. Other novel multitargeted tyrosine kinase inhibitors (pazopanib and axitinib) and mTOR inhibitors (everolimus) are in clinical development. Recently reported and ongoing clinical trials will help further define the role of these agents as therapy for metastatic RCC. [Pubmed] [Scholar] [EndNote] [BibTex]
30-Oct-2007 - Nexavar’s Differentiated Mechanism
Nexavar’s Differentiated Mechanism
Nexavar targets both the Tumour cell and Tumour vasculature. In preclinical studies, Nexavar has been shown to target members of two classes of kinases known to be involved in both cell proliferation (growth) and angiogenesis (blood supply) – two important processes that enable cancer growth.
These kinases included Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET. Preclinical models have also demonstrated that Raf/MEK/ERK has a role in HCC. Therefore, blocking signaling through Raf-1 may offer therapeutic benefits in HCC.
Nexavar is currently approved in more than 50 countries, including the United States and the European Union, for the treatment of patients with advanced Kidney Cancer. In Europe, Nexavar is approved for the treatment of patients with advanced renal cell carcinoma (RCC) who have failed prior Interferon-alpha or Interleukin-2 based therapy or are considered unsuitable for such therapy.
Nexavar is also being evaluated by the companies, international study groups, government agencies, and individual investigators as a single agent or combination treatment in a wide range of other cancers, including adjuvant therapy for Kidney Cancers, metastatic melanoma, breast cancer and non-small cell lung cancer (NSCLC).
To view the original of this article Click Here
07-Sep-2007 - sorafenib in clear-cell renal cell carcinoma: a Phase III overview.
Expert Rev Anticancer Ther. 2007 Sep ;7 (9):1193-202 17892420
Safety and tolerability of sorafenib in clear-cell renal cell carcinoma: a Phase III overview.
[My paper] Thomas E Hutson
This review summarizes the safety of sorafenib, an oral multikinase inhibitor, focusing on the randomized, placebo-controlled, Phase III Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) in renal cell carcinoma, which formed the basis of the approval of sorafenib.
Similar to other targeted agents, sorafenib acts primarily to induce disease stabilization, rather than tumor regression, suggesting that long-term administration is necessary.
The tolerability of an agent is important in long-term treatment, and a predictable and manageable side-effect profile is advantageous. Although IL-2 and interferon have been standard care treatments for advanced renal cell carcinoma for over a decade, they are poorly tolerated.
Targeted agents offer an alternative for patients with advanced renal cell carcinoma, as initial therapy or after failure of cytokine treatment. [Pubmed] [Scholar] [EndNote] [BibTex]
06-Jul-2007 - N.I.C.E. Press Release of 06-Jul-2007
ISSUED: 6 July 2007
PRESS STATEMENT
N.I.C.E. welcomes new topic referral
- CUT** as NOT relevant to Urological Cancers or related matters.**
• 1 technology for appraisal as part of NICE’s multiple technology appraisal (MTA) programme on: o Bevacizumab, sorafenib tosylate and sunitinib for renal cell carcinoma.
- CUT** as NOT relevant to Urological Cancers or related matters.**
Commenting on the referrals, Andrew Dillon, NICE Chief Executive said: “NICE welcomes the referral of today’s topics, which address areas of significant concern for those working in the NHS, patients and carers.
We are keen to begin developing guidance that will help to inform their decisions about treatment and healthcare in these areas as soon as possible and we will publish details of the timetables for these topics on our web site shortly.” Ends
To view the whole of this N.I.C.E. document in its original form in .PDF Click Here
11-Jan-2007 - Sorafenib in Advanced Clear-Cell Renal-Cell Carcinoma.
N Engl J Med. 2007 Jan 11;356 (2):125-134 17215530
Sorafenib in Advanced Clear-Cell Renal-Cell Carcinoma.
[My paper] Bernard Escudier , Tim Eisen , Walter M Stadler , Cezary Szczylik , Stéphane Oudard , Michael Siebels , Sylvie Negrier , Christine Chevreau , Ewa Solska , Apurva A Desai , Frédéric Rolland , Tomasz Demkow , Thomas E Hutson , Martin Gore , Scott Freeman , Brian Schwartz , Minghua Shan , Ronit Simantov , Ronald M Bukowski
BACKGROUND: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of sorafenib, a multikinase inhibitor of tumor-cell proliferation and angiogenesis, in patients with advanced clear-cell renal-cell carcinoma.
METHODS: From November 2003 to March 2005, we randomly assigned 903 patients with renal-cell carcinoma that was resistant to standard therapy to receive either continuous treatment with oral sorafenib (at a dose of 400 mg twice daily) or placebo; 451 patients received sorafenib and 452 received placebo.
The primary end point was overall survival. A single planned analysis of progression-free survival in January 2005 showed a statistically significant benefit of sorafenib over placebo. Consequently, crossover was permitted from placebo to sorafenib, beginning in May 2005.
RESULTS: At the January 2005 cutoff, the median progression-free survival was 5.5 months in the sorafenib group and 2.8 months in the placebo group (hazard ratio for disease progression in the sorafenib group, 0.44; 95% confidence interval [CI], 0.35 to 0.55; P<0.01).
The first interim analysis of overall survival in May 2005 showed that sorafenib reduced the risk of death, as compared with placebo (hazard ratio, 0.72; 95% CI, 0.54 to 0.94; P=0.02), although this benefit was not statistically significant according to the O'Brien-Fleming threshold.
Partial responses were reported as the best response in 10% of patients receiving sorafenib and in 2% of those receiving placebo (P<0.001). Diarrhea, rash, fatigue, and hand-foot skin reactions were the most common adverse events associated with sorafenib. Hypertension and cardiac ischemia were rare serious adverse events that were more common in patients receiving sorafenib than in those receiving placebo.
CONCLUSIONS: As compared with placebo, treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma in whom previous therapy has failed; however, treatment is associated with increased toxic effects.
(ClinicalTrials.gov number, NCT00073307.) Copyright 2007 Massachusetts Medical Society. [Pubmed] [Scholar] [EndNote] [BibTex] [Doi]
15-Dec-2006 -Melanoma- Phase III Trial Of Nexavar In Patients With Advanced Melanoma Does Not Meet Primary Endpoint
The latest Trial III data is at:
and makes an interesting read (if you have a high tedium threshold!!!)
Phase III Trial Of Nexavar In Patients With Advanced Melanoma Does Not Meet Primary Endpoint
Main Category: Dermatology News Article Date: 05 Dec 2006 - 0:00 PDT
OR for RCC: Click Here
OR for Trial Results for RCC: Click Here which starts out: Bayer And Onyx Announce Pivotal Nexavar Kidney Cancer Study Published In NEJM Main Category: Cancer / Oncology News Article Date: 15 Jan 2007 - 20:00 PDT
Bayer Pharmaceuticals Corporation (NYSE: BAY) and Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) has announced that the New England Journal of Medicine has published their pivotal Phase III trial demonstrating that Nexavar® (sorafenib) tablets doubled median progression-free survival (PFS) in patients with advanced renal cell carcinoma (RCC), or Kidney Cancer. The data, as assessed by independent radiologic review, are from the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) - the largest randomized controlled trial ever conducted in advanced RCC.
"Historically, patients with kidney cancer have had limited treatment options and there has been a particularly critical need for new therapies to help patients with advanced disease," said co-principal investigator Ronald Bukowski, M.D.,**CUT**
Nexavar(R) (sorafenib) tablets is a registered trademark of Bayer Pharmaceuticals Corporation.
Bayer Pharmaceuticals Corporation Click Here
24-Apr-2006 - Phase II Trial of Sorafenib
J Clin Oncol. 2006 Apr 24; : 16636341
Phase II Placebo-Controlled Randomized Discontinuation Trial of Sorafenib in Patients With Metastatic Renal Cell Carcinoma.
[My paper] Mark J Ratain , Tim Eisen , Walter M Stadler , Keith T Flaherty , Stan B Kaye , Gary L Rosner , Martin Gore , Apurva A Desai , Amita Patnaik , Henry Q Xiong , Eric Rowinsky , James L Abbruzzese , Chenghua Xia , Ronit Simantov , Brian Schwartz , Peter J O'dwyer
PURPOSE: This phase II randomized discontinuation trial evaluated the effects of sorafenib (BAY 43-9006), an oral multikinase inhibitor targeting the tumor and vasculature, on tumor growth in patients with metastatic renal cell carcinoma.
PATIENTS AND METHODS: Patients initially received oral sorafenib 400 mg twice daily during the initial run-in period. After 12 weeks, patients with changes in bidimensional tumor measurements that were less than 25% from baseline were randomly assigned to sorafenib or placebo for an additional 12 weeks; patients with >/= 25% tumor shrinkage continued open-label sorafenib; patients with >/= 25% tumor growth discontinued treatment. The primary end point was the percentage of randomly assigned patients remaining progression free at 24 weeks after the initiation of sorafenib.
RESULTS: Of 202 patients treated during the run-in period, 73 patients had tumor shrinkage of >/= 25%. Sixty-five patients with stable disease at 12 weeks were randomly assigned to sorafenib (n = 32) or placebo (n = 33). At 24 weeks, 50% of the sorafenib-treated patients were progression free versus 18% of the placebo-treated patients (P = .0077). Median progression-free survival (PFS) from randomization was significantly longer with sorafenib (24 weeks) than placebo (6 weeks; P = .0087). Median overall PFS was 29 weeks for the entire renal cell carcinoma population (n = 202). Sorafenib was readministered in 28 patients whose disease progressed on placebo; these patients continued on sorafenib until further progression, for a median of 24 weeks. Common adverse events were skin rash/desquamation, hand-foot skin reaction, and fatigue; 9% of patients discontinued therapy, and no patients died from toxicity.
CONCLUSION: Sorafenib has significant disease-stabilizing activity in metastatic renal cell carcinoma and is tolerable with chronic daily therapy. [Pubmed] [Scholar] [EndNote] [BibTex]
Side Effects
Below are some of the side effects that have been noted by users of the drug. Please ensure that you take proper medical advice before tyring any of these as each person is different.
Hand Foot Syndrome
Bathe feet in warm salt water, towel dry. apply glycerine/icthamol on soaked cotton wool balls. Use melolite to cover. If toes need to be treated use tubegauze. When inflamation has gone skin can be PROFESSIONALLY PAIRED BY A CHIROPODIST!! DO NOT PEEL SKIN YOURSELF!
Take care, God bless. Antoinette (Team Angelena)
I have also heard that Udder Cream available from any farm suppliers is exellent with side effects: the burning, itching and peeling that occurs with both hands and feet for some users.Udder Cream contains NO perfumes etc. thus is hypoallergenic.
Also that it may help to wear cotton socks or/and gloves to cover the hands and feet letting the udder cream remain in concentration longer. Do be carefull of peeling skin never pull it off as that will risk an open wound; cut away easily separated skin with sharp scissors, avoid pulling or tearing.
Good Luck - User: Greg L-W.
Reflux
Manuka Honey (10 plus must say UMF on jar) is good for relieving reflux from Nexavar.
Hope this helps someone.
Take care, God bless. Antoinette (Team Angelena)
References
|
Disclaimer
Kidney Cancer Resource (KCR) is not influenced by sponsors. The information contained herein is not intended as a substitute for the advice of an appropriately qualified and licensed physician or other licensed health care provider. The information provided here is for educational and information purposes only. Early accurate Diagnosis (Dx.) saves lives. Please check with a physician if you suspect you are ill, never ignore Symptoms. To help your health care specialist make an accurate Diagnosis please keep notes of dates, times and details of your Symptoms. We are not offering medical advice nor do we consider links, individuals or articles accessed through this site to be offering medical advice.
E&OE - Errors & Omissions Excepted
As much of the information posted on this Web Site for peoples convenience is of a medical or technical nature, and may be a matter of life or death the E&OE is a Disclaimer showing that to the best of our ability information is accurate and correctly written or transcribed. Before acting on information on this site you are responsible for checking it with your relevant medical team. We can not be held responsible for any Errors & Omissions made; nor for information on links and articles provided in good faith.
