Zytiga is a potent CYP17 inhibitor that works by preventing the biosynthesis of all androgens in the body. Resistance to Zytiga is a serious problem in urology leaving few alternative options post Zytiga. Resistance to Zytiga is believed to be mediated by the PI3K and Akt signalling pathway and 2 drugs (GDC0980 and GDC0068 respectively) that are inhibitors of these 2 molecular targets are under clinical investigation in combination with Zytiga.
Salvestrol Q40 has been shown to be a potent inhibitor of the PI3K/Akt signalling pathway, and itself has powerful anticancer effects mediated by the enzyme CYP1B1. Salvestrol Platinum contains a very high concentration of salvestrol Q40 and this supplement would potentiate the activity of Zytiga in metastatic tumour regression activity as well as providing prevention against PI3K/Akt mediated Zytiga resistance. One capsule daily of Salvestrol Platinum is sufficient for prevention of Zytiga resistance but higher doses up to 6 capsules daily can be used for maximum combined therapeutic effect.
Thursday, 17 May 2012
Zytiga with Low Dose Prednisone
In a clinical study at the Dana Farber Institute in the USA, researchers used half the dose of prednisone (a steroid) standardly given with abiraterone acetate. This lower dose (5 mg), it is hoped, would reduce the side effects associated with steroids while maintaining its benefits of protecting particular steroid imbalances associated with abiraterone. Since there were no increased side effects from abiraterone, the researchers feel that the lower dose of prednisone (5mg daily) is adequate for most patients.
"Most of the patients in this study had large tumors, high grade prostate cancers and were at high risk for cancer spread," Taplin remarks. "We're very encouraged by the results."
These results show that Zytiga can be safely taken with low dose prednisone (5 mg daily) to good effect, and that the low dose of prednisone is sufficient to prevent the side effects from Zytiga that result from corticosteroid imbalance.
Clinical Study Shows Zytiga Eliminates Prostate Tumours
The hormone-depleting drug Zytiga (Abiraterone Acetate) approved last year for the treatment of metastatic prostate cancer can help eliminate or nearly eliminate tumors in many patients with aggressive cancers that have yet to spread beyond the prostate, according to a clinical study to be presented at the annual meeting of the American Society of Clinical Oncology (ASCO), June 1-5, in Chicago.
The phase II clinical trial, led by investigators at Dana-Farber Cancer Institute and other research centers, examined the use of the drug abiraterone acetate (Zytiga) in combination with prednisone and surgery in 58 men with high-risk prostate cancer isolated to the prostate gland. Participants received either three or six months of the two-drug regimen followed by surgery to remove the prostate. When the treatment was complete, pathology exams showed that one-third of the participants had no or almost no tumor tissue left.
"Very high-risk cancers localized to the prostate are rarely cured by prostatectomy alone," says the study's lead author, Mary-Ellen Taplin, MD, of Dana-Farber. "Therapies that combine surgery with the older androgen-inhibiting drugs have not historically improved outcomes. This unmet need has given rise to efforts to develop new drugs such as Zytiga capable of more completely reducing androgen levels within the prostate tumors."
Taplin will present the data (abstract 4521) on Saturday, June 2, at , Arie Crown Theater,
McCormick Place
.
Androgen, the male hormone, provides the fuel for prostate cancer growth. Conventional therapies target androgen production in the testes and adrenal glands, but not within the tumor itself. Abiraterone acetate is capable of blocking androgen production in all three sites.
In the study, researchers used half the dose of prednisone (a steroid) standardly given with abiraterone acetate. This lower dose, it is hoped, would reduce the side effects associated with steroids while maintaining its benefits of protecting particular steroid imbalances associated with abiraterone. Since there were no increased side effects from abiraterone, the researchers feel that the lower dose of prednisone (5mg daily) is adequate for most patients.
"Most of the patients in this study had large tumors, high grade prostate cancers and were at high risk for cancer spread," Taplin remarks. "We're very encouraged by the results and have begun another phase II study investigating another novel androgen signaling inhibitor, MDV3100, in the neoadjuvant setting for high risk prostate cancer. We are also developing a clinical trial program investigating the addition of the investigational drug ARN509 to abiraterone. To prove the overall benefit of intensive androgen deprivation treatment in conjunction with prostatectomy, a large randomized clinical trial will need to be done."
Wednesday, 16 May 2012
Zytiga Recommended for use on the NHS
A drug to treat advanced prostate cancer should be given to patients on the NHS, a health watchdog has said.
Abiraterone, marketed as Zytiga, can extend the lives of late-stage cancer sufferers by more than three months.The National Institute for Health and Clinical Excellence (Nice) revised its recommendations after fresh information from manufacturer Janssen, and the new draft guidance was welcomed by experts.
Professor Alan Ashworth, chief executive of the Institute of Cancer Research, said: "We are delighted by today's decision to allow patients with advanced prostate cancer to receive abiraterone on the NHS.
"This drug was discovered at the Institute of Cancer Research (ICR) and is the result of more than two decades of dedicated work by our scientists and collaborators.
"In clinical trials of men with advanced prostate cancer who have already tried chemotherapy, it has been shown to extend life by an average of four months and improve quality of life."
Cally Palmer, chief executive of The Royal Marsden NHS Foundation Trust, said: "The development of abiraterone by The Royal Marsden and the ICR highlights the national importance of funding pioneering cancer research.
"We are delighted our patients at The Royal Marsden were among the first to benefit from the very latest in drug development and are pleased that patients across the country will now also benefit from our work."
Each year around 37,000 men in the UK are diagnosed with prostate cancer and 10,000 die from the disease. It is the second most common cause of cancer death in men - after lung cancer - accounting for 13%.
This drug was discovered by Professor Gerry Potter at the Institute of Cancer Research and is the result of more than two decades of dedicated work by our scientists and collaborators.Professor Alan Ashworth
Sir Andrew Dillon, chief executive of Nice, said: "During the consultation on the draft guidance Janssen, the manufacturer of the drug, submitted further information for the committee to consider.
"This included a revised patient access scheme which involves providing the drug to the NHS at a discounted price, further information on which patients would benefit most and clarification on how many patients could receive the drug.
"These factors enabled the committee to revise its preliminary recommendation and now recommend the drug for use on the NHS.
"We are very pleased that Janssen's submission to our consultation means that we are able to produce draft guidance recommending abiraterone - it is an effective treatment, potentially extending life by more than three months, and it also allows patients to be treated at home as it can be taken orally."
NICE Recommend Zytiga
NICE have today issued a final appraisal document recommending Zytiga for use on the NHS which states "Abiraterone in combination with prednisone is recommended as an option for the treatment of castration resistant metastatic prostate cancer".
Prostate cancer wonder drug set for approval in England
- Final approval of abiraterone for England and Wales expected in June
- Prostate cancer charity calls on Scotland to approve drug
A drug to treat advanced prostate cancer should be given to patients in England and Wales, according to the NHS rationing body.
Abiraterone, marketed as Zytiga, can extend the lives of late-stage cancer sufferers by more than three months.
The National Institute for Health and Clinical Excellence (Nice) had originally rejected the drug, which costs around £3,000 a month, for not being cost effective.
It provoked an angry response from both patients and cancer charities.
However, today it revised its recommendations after the manufacturer Janssen offered the tablet at a lower undisclosed price.
If Nice gives final approval to the drug it will have to be offered by the NHS in England and Wales from June.
However, in a reverse of the usual trend the drug won't be available in Scotland. In March the Scottish Medicines Consortium turned the drug down saying the cost of abiraterone did not justify the health benefits. This decision could change as it is still in talks with Janssen.
The new draft guidance has been welcomed by experts.
Owen Sharp, Chief Executive of The Prostate Cancer Charity, said: 'This announcement represents a resounding triumph for each of the thousands of men with advanced prostate cancer in England and Wales who know just how much the prospect of precious extra time with their loved ones really means.
'Although today marks a very welcome advancement, it has to be remembered that abiraterone remains out of reach to men in Scotland on the NHS. We need to see every man who needs this drug receive it on the NHS, regardless of where they live in the UK.'
Each year around 37,000 men in the UK are diagnosed with prostate cancer and 10,000 die from the disease. It is the second most common cause of cancer death in men, accounting for 13 per cent.
Sir Andrew Dillon, chief executive of NICE, said: 'During the consultation on the draft guidance Janssen, the manufacturer of the drug, submitted further information for the committee to consider.
'This included a revised patient access scheme which involves providing the drug to the NHS at a discounted price, further information on which patients would benefit most and clarification on how many patients could receive the drug.
'These factors enabled the committee to revise its preliminary recommendation and now recommend the drug for use on the NHS.
'We are very pleased that Janssen's submission to our consultation means that we are able to produce draft guidance recommending abiraterone - it is an effective treatment, potentially extending life by more than three months, and it also allows patients to be treated at home as it can be taken orally.'
Professor Alan Ashworth, chief executive of the Institute of Cancer Research, said: 'We are delighted by today's decision to allow patients with advanced prostate cancer to receive abiraterone on the NHS.
'This drug was discovered by Professor Gerry Potter at the Institute of Cancer Research and is the result of more than two decades of dedicated work by our scientists and collaborators.
'In clinical trials of men with advanced prostate cancer who have already tried chemotherapy, it has been shown to extend life by an average of four months and improve quality of life.'
NICE recommended the use of abiraterone in combination with prednisone or prednisolone for the treatment of castration-resistant metastatic prostate cancer that has progressed after one docetaxel-containing therapy.
Victory for Zytiga
Approval of Zytiga by NICE for use on the NHS for the treatment of metastatic prostate cancer is a victory for all those who have worked hard to develop this medication.
Tuesday, 15 May 2012
Chemotherapy and Salvestrols
I am really interested in following this discussion. My dad is a prostate cancer patient, so I'm interested in your story. I have been researching a lot of these up-coming drugs, and according to a pharma strategy blog, I have been reading TAK 700 has a similar mechanism of action to Abiraterone, but may allegedly be superior... although the jury may not be out on that one yet (as far as the trials are concerned).
My dad was on a trial for MDV3100 which didn't work for him but he may have been on the placebo arm, or his PCa is hormone refractory and not receptive to the drug... It's worth considering whether there is a placebo arm or not when entering a trial as that is the risk that you are taking on. Also it's worth considering about how your oncologist is and whether they will pull you from the trial if it's not working for you. They are not supposed to, but you probably have an idea of how much your oncologist has your back...
I have a question. My dad is on taxotere right now, has just completed 3 cycles. First diagnosed 1998, RP 1999, remission until late 2008, radiotherapy 2009, androgen blockade 2010, MDV3100 trial 2011, docetaxel 2012. How much damage does docetaxel/taxotere really do? I understood it was one of the more "gentle" chemos, and certainly the dosage for mCRPC is 25% lower than for metastatic advanced breast cancer (75mg/m2 vs 100mg/m2). Is there anything he can do to help deal with the liver damage. I believe all his tests are coming back ok. Someone recommended milk thistle. Any thoughts on this?
Also, I would like to encourage him to take salvestrols. Could you provide a link & recommendation for purchase? His PSA pre-chemo was 17, post chemo 9 and then 10, so I am not sure how effective it is so I think we need to start looking at alternatives. I would appreciate any advice really. He is pretty hard to persuade and usually only responds to things that have demonstrated scientific effectiveness to randomised blinded testing. He was an engineer/trained as a physicist and is extremely cynical and untrusting, so persuading him is hard. And he doesn't really subscribe to big-pharma conspiracy theory...
One last question, any thoughts on the issue of refined sugar consumption feeding tumour growth, and fructose (or HFCS) related liver damage, and whether these are significant concerns/factors for a PCa patient?
Any help and advice much appreciated
Best wishes
Hannah
Is it safe to combine salvestrols with chemotherapy
Answer:
Docetaxel is a classic cytotoxic chemotherapy agent that is toxic to normal cells as well as the cancer cellls. It is therefore toxic to other normal cells such as liver cells and consequently is hepatotoxic. Milk thistle can help with the liver and does itself contain salvestrols.
TAK-700 (Orteronel) is similar to Zytiga (Abiraterone) because it works by inhibiting the enzyme CYP17. However it is a weaker inhibitor than Zytiga and there is an important difference between them in that Zytiga is an irreversible inhibitor whilst the inhibition with TAK-700 is reversible. This means that clinically Zytiga is much more efficient at inhibiting the CYP17 enzyme and causes total androgen blockade which TAK-700 is not able to do. So TAK-700 is a weaker partial inhibitor of CYP17 compared to Zytiga which is a potent and irreversible inhibitor.
Salvestrols can safely be taken alongside hormonal therapy agents such as Zytiga and TAK-700. The recomended dose here is 6000 points per day.
Salvestrols can also be safely taken alongside other medications such as chemotherapy. There are clinical results from China which show that Salvestrol Q40 reduces the side effects from taxotere chemotherapy and increases the anticancer effects.
On the days receiving chemotherapy the recommended dose is 2000 points. In the recovery period the dose can be increased to 6000 points daily for maximum effect.
My dad was on a trial for MDV3100 which didn't work for him but he may have been on the placebo arm, or his PCa is hormone refractory and not receptive to the drug... It's worth considering whether there is a placebo arm or not when entering a trial as that is the risk that you are taking on. Also it's worth considering about how your oncologist is and whether they will pull you from the trial if it's not working for you. They are not supposed to, but you probably have an idea of how much your oncologist has your back...
I have a question. My dad is on taxotere right now, has just completed 3 cycles. First diagnosed 1998, RP 1999, remission until late 2008, radiotherapy 2009, androgen blockade 2010, MDV3100 trial 2011, docetaxel 2012. How much damage does docetaxel/taxotere really do? I understood it was one of the more "gentle" chemos, and certainly the dosage for mCRPC is 25% lower than for metastatic advanced breast cancer (75mg/m2 vs 100mg/m2). Is there anything he can do to help deal with the liver damage. I believe all his tests are coming back ok. Someone recommended milk thistle. Any thoughts on this?
Also, I would like to encourage him to take salvestrols. Could you provide a link & recommendation for purchase? His PSA pre-chemo was 17, post chemo 9 and then 10, so I am not sure how effective it is so I think we need to start looking at alternatives. I would appreciate any advice really. He is pretty hard to persuade and usually only responds to things that have demonstrated scientific effectiveness to randomised blinded testing. He was an engineer/trained as a physicist and is extremely cynical and untrusting, so persuading him is hard. And he doesn't really subscribe to big-pharma conspiracy theory...
One last question, any thoughts on the issue of refined sugar consumption feeding tumour growth, and fructose (or HFCS) related liver damage, and whether these are significant concerns/factors for a PCa patient?
Any help and advice much appreciated
Best wishes
Hannah
Is it safe to combine salvestrols with chemotherapy
Answer:
Docetaxel is a classic cytotoxic chemotherapy agent that is toxic to normal cells as well as the cancer cellls. It is therefore toxic to other normal cells such as liver cells and consequently is hepatotoxic. Milk thistle can help with the liver and does itself contain salvestrols.
TAK-700 (Orteronel) is similar to Zytiga (Abiraterone) because it works by inhibiting the enzyme CYP17. However it is a weaker inhibitor than Zytiga and there is an important difference between them in that Zytiga is an irreversible inhibitor whilst the inhibition with TAK-700 is reversible. This means that clinically Zytiga is much more efficient at inhibiting the CYP17 enzyme and causes total androgen blockade which TAK-700 is not able to do. So TAK-700 is a weaker partial inhibitor of CYP17 compared to Zytiga which is a potent and irreversible inhibitor.
Salvestrols can safely be taken alongside hormonal therapy agents such as Zytiga and TAK-700. The recomended dose here is 6000 points per day.
Salvestrols can also be safely taken alongside other medications such as chemotherapy. There are clinical results from China which show that Salvestrol Q40 reduces the side effects from taxotere chemotherapy and increases the anticancer effects.
On the days receiving chemotherapy the recommended dose is 2000 points. In the recovery period the dose can be increased to 6000 points daily for maximum effect.
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