Tuesday 31 July 2012

ZRPC a New Term in Prostate Cancer Oncology

Zytiga Resistant Prostate Cancer (ZRPC) is emerging as a distinct form of prostate cancer that is completely androgen independant. Zytiga works to block all androgen production in the human body by selectively inhibiting the cytochrome P450 enzyme CYP17. When a patient has become Zytiga resistant then the prostate cancer must be able to survive in the complete absence of androgens. At this stage for the cancer to be progressing the tumour cells must have evolved a means of survival and growth in the absence of androgens. Thus ZRPC is the ultimate form of castrate resistant prostate cancer CRPC.

Zytiga resistance is believed to be mediated by mutations in the androgen receptor through splice varients that can result in permanantly signalling androgen receptors. One splice varient is thought to have no ligand binding domain and can signal to grow without androgen stimulation. So blocking androgens is useless for this type of cancer, but you do not know if you have this type of cancer until you have tried Zytiga and become resistant i.e classified as ZRPC.

What are the treatment options for Zytiga Resistant Prostate Cancer (ZRPC) ?

1. Salvestrol Platinum 2000

2. Cabozantinib XL-184

3. Enzalutamide MDV3100

4. Quercetin

5. Bromelain

6. Trametinib

7. Pazopanib

8. Graviola

9. Regorafenib

Why is Dendreon Running Scared of Zytiga ?

Dendreon Corp manufacture Provenge the biggest flop in prostate cancer oncologies history. Provenge does not even lower PSA and may even promote metastatic spread to the bones.

There is one big difference between Zytiga and Provenge - Zytiga works and Provenge doesn't.

Every case reported on cancer patient discussion websites descibes Provenge as a failure. So why is Dendreon Corp running scared of Zytiga ?

This is because Provenge is licensed for metastic castrate resistant prostate cancer mCRPC which is asymptomatic or mildly symptomatic. Once Zytiga has been started together with Prednisone then Provenge can no longer be given since it would be rendered useless in the prescence of the immunosuppresive corticosteroid Prednisone. A patient would have to come off the Zytiga Prednisone combo (ZPC) and have a 30 day washout period before the Provenge treatment could be started. Aye - but heres the rub.

A patinet will only come off Zytiga if they are Zytiga resistant, and for this to be clinically verified 3 criteria are needed to be fulfilled.

1. A PSA increase of greater than 25 %.
2. Radiological evidence of disease progression.
3. Symptomatic progression

Aye - and here the double whammy

If a patient has symptomatic progression they no longer qualify for Provenge !

So basically once a patient starts on Zytiga they are removed from the Dendreon pool of potential customers. Dendreon can see their customer pool evaporating before them as Zytiga eats into the market taking large chunks at a time. By the time Dendreon reaches Europe the word will be out that it is useless and governmental drug rationing bodies like NICE in the UK would scoff at a quote for $ 93,000 dollars for doing what exactly ? You won't convince the Wittig Council for Drug Rationing in Germany either. So the Dendreon pool is evaporating before them like a mirage of a market that never was because their treatment simply does not work.

Pomegranate Juice Slows PSA Increase

A Phase 2 clinical study on Pomegranate Juice (PJ) on men with stage 1 prostate cancer showed that the rate of increase of PSA levels in these men decreased more than 3 fold from a doubling time of 15 months without PJ, lengthening to 54 months for those who drank PJ.

This means that PJ, along with other fruit juices such as grape and orange, can slow the rate of development of prostate cancer. The scientific reason for this cancer reducing effect is thought to be due to the relatively high levels of cancer fighting salvestrols in pomegranate juice estimated at 10 points (1mg) per glass of pure juice. The gerson diet has been shown to be active against a variety of cancers including advanced prostate cancer and this diet is based upon juicing organic fuits and vegetables and can supply upto 100 points (10mg) of salvestrols per killogram of fresh produce.

Could this finding be developed into a therapy for prostate cancer ?

Yes, but you need much higher doses of at least 1000 points (100 mg) to tackle advanced stage disease.

This has been achieved with the development of salvestrol platinum in strengths of 1000 and 2000 points.

Friday 27 July 2012

Zytiga Approved in Northern Ireland

Breakthrough prostate cancer drug Zytiga approved for use in Northern Ireland

The Drug abiraterone acetate (Zytiga) – a breakthrough treatment for advanced prostate cancer – has been approved for use in Northern Ireland it was announced this morning Friday 27 July 2012.

Abiraterone is a new type of hormone therapy for men with advanced prostate cancer that has stopped responding to other hormone therapy and chemotherapy treatments.
Studies on abiraterone show that it can prolong the life of men in the final stages of prostate cancer and improve the quality of their lives.
In May, Foyle MP Mark Durkan put pressure on Health Minister Edwin Poots to urge approval for the use of the drug following a National Institute for Health and Clinical Excellence (NICE) recommendation that abiraterone should be made available on the NHS in England and Wales.
Mr Durkan, who has also supported The Prostate Cancer Charity’s campaign at Westminster for the approval of abiraterone, said:
“This is great news and an excellent outcome for men with advanced prostate cancer in Northern Ireland.
“Great credit should be given to the campaigning of The Prostate Cancer Charity and its supporters.
“Following NICE’s acceptance in May that abiraterone should be treated as an ‘end of life’ drug they decided to overturn their draft decision not to fund the drug generally on the NHS in England and Wales.
“Eager to see the implementation of NICE’s recommendation by the Department of Health here, I wrote to Edwin Poots requesting he gave due consideration to NICE’s decision – urging the Minister to approve abiraterone for use in the North as soon as possible.
“I therefore welcome confirmation from the Department of Health that they have endorsed the NICE guidance as applicable in Northern Ireland from this week – 24 July 2012.”
Bryan Jones, Policy and Campaigns Manager for The Prostate Cancer Charity thanked Mr Durkan saying:
“Your support for our campaign in recent months has been vital in helping to achieve this outcome. Thank you for your work on behalf of men with prostate cancer throughout the UK – not least in Northern Ireland.”

Sunday 22 July 2012

83% of Medical Oncologist Prescribe Zytiga for Prostate Cancer




BioTrends Research Group has released findings from the second wave of its Zytiga (abiraterone acetate) report, in which a total of 121 U.S. urologists and medical oncologists were surveyed about their current awareness, trial and usage of Janssen Biotech’s Zytiga for discrete metastatic castrate-resistant prostate cancer (MCRPC) patient populations.

The study was fielded one year post launch of Zytiga in the United States and finds that surveyed medical oncologists are currently more experienced with prescribing Zytiga compared with urologists; 83 percent of surveyed oncologists have prescribed Zytiga in clinical practice compared with 40 percent of surveyed urologists. These rates of usage have increased in both specialist groups compared with BioTrends’ first wave of research (carried out six months post launch of Zytiga) where 70 percent and 23 percent of oncologists and urologists, respectively, had prescribed Zytiga in clinical practice.

Compared with the first wave of research, oncologists now report a greater perceived efficacy of Zytiga in MCRPC patients pre-treated with docetaxel (Sanofi’s Taxotere, generics). Of those oncologists that are aware of Zytiga, the perceived overall survival achievement of Zytiga increased from 10.37 months in wave 1 to 11.01 months in wave 2. Similarly, amongst surveyed oncologists the reported time to prostate-specific antigen (PSA) progression increased wave-over-wave (7.0 vs. 7.9 months, respectively). However, oncologists still underestimate Zytiga’s performance compared with what has been demonstrated in pivotal clinical trials in the post-docetaxel setting. Nevertheless, wave-on-wave, the majority of surveyed physicians say that they have seen decreased use of mitoxantrone (Pfizer Novantrone, generics), and more than a third report decreased use of Sanofi’s Jevtana (cabazitaxel).

Janssen recently filed for FDA approval for Zytiga in the asymptomatic/minimally symptomatic, chemotherapy-naïve MCRPC setting; interviewed physicians are optimistic about Zytiga in this setting. In this wave of research, 20 percent of surveyed physicians have noticed a decrease in the use of Dendreon’s Provenge in the pre-chemotherapy MCRPC setting. The majority (79 percent), of all surveyed physicians believe that Zytiga approval in the first-line asymptomatic/minimally symptomatic MCRPC setting is likely or extremely likely. A greater proportion of oncologists believe approval is likely or extremely likely compared with urologists in both waves of research (83 percent vs. 75 percent in wave 2).

Although the majority of surveyed physicians are unaware of products that are in development for the treatment of MCRPC, of those that are, most point to Astellas/Medivation’s enzalutamide (formerly MDV-3100), Algeta/Bayer Healthcare’s Alpharadin and Exelixis’s Cabozantinib. Furthermore, more than a third of surveyed physicians select enzalutamide (formerly MDV-3100) as one of the top three emerging therapies that will pose the biggest competitive threat to Zytiga in the treatment of MCRPC. However concerns remain over Enzalutamides cardiotoxicity problems.

Future Projections for Zytiga Use in Prostate Cancer Therapy

Projected Zytiga Treatment of Various Stages of Prostate Cancer


Early Stage

Present: LHRH agonists Zoladex, Lupron                  Future: Low dose Zytiga


Medium Stage

Present: Casodex (Bicalutamide), Ketoconazole         Future: MDV3100 (Enzalutamide), Zytiga


Advanced Stage (metastatic)

Present: Docetaxel (Taxotere)                                    Future: Docetaxel, Jevtana (Cabazitaxel)


Post Chemo

Present: Zytiga                                                           Future: Zytiga


Post Zytiga (Zytiga Refractory)

Present: Jevtana                                                         Future: Cabozantinib

Zytiga as Neoadjuvant Single Agent Therapy

Presently Zytiga has been clinically trialled to show a greater than 30% response rate in the elimination of tumours when tried early on in the neoadjuvant setting in combination with Lupron injections.

Since Zytiga can work as a single agent to reduce testosterone levels to zero on its own there seems to be little point to using Lupron, and this raises the question "Should Zytiga be used as a front line agent taken with prednisone alone".

Lupron injections work at the adrenal axis to lower plasma testosterone via an LHRH feedback mechanism. However this does not reduce testosterone produced by the prostate cancer cells, but Zytiga does. So there is no logical reason to include Lupron at all, and the Zytiga plus Prednisone combo should work just as effectively on its own.

Clinical trials need to be conducted on this and should look at the use of low dose zytiga (one 250 mg tablet) daily taken shortly after eating, together with 5 mg of prednisone taken 4 hours later as first line neoadjuvant therapy for early stage prostate cancer.

Saturday 21 July 2012

Could Zytiga Top $ Billion Dollar Sales in 2012 ?

Zytiga is set for "Blockbuster" status if it can make more than a $ billion dollar sales in its first full year of trading. Zytiga was only approved for sales by the FDA in April 2011 and first quarter sales reached $ 55 million worldwide. 2012 is the first full year of trading for Zytiga, and by the first quarter of 2012 sales had reached $ 200 M, and the second quarter reached $ 232 M, making a whopping total of $ 432 M for the first half of 2012. Projected sales are $ 275 M for the next quarter and $ 325 M for the final quarter making a projected total sales of Zytiga for 2012 at $ 1,032 M just reaching the billion dollar mark. If these projections are borne out, and some say they are conservative estimates and actual sales may be much higher than this, then Zytiga can be classified as a blockbuster drug.

Monday 16 July 2012

Does Provenge Promote Prostate Cancer ?

Provenge is an immunotherapy treatment for prostate cancer that is solely available in the United States. What is the evidence that Provenge works and does it even lower PSA levels. The evidence for its efficacy comes from a Phase 3 clinical study on mildly asymptomatic prostate cancer patients who had not received chemotherapy. Thos receiving Provenge lived for an average time of 25.9 monthst whilst the control arm receiving the provenge placebo injections lived for 21.4 months. In the recent Zytiga trial the median survival time for the drug treated arm was greater than 30 months and the placebo control arm had a survival of 27.2 months. Taken together these result suggest a. increase of over 4 months survival taking Zytiga compared to Provenge.

Provenge is great in theory - get the body to fight the cancer cells using the immune system - but what about the clinical reality of using this approach. In reality many men undergoing Provenge treatment experience a rise in PSA levels and measurable spread of the prostate cancer to the bones. Could this treatment be actually stimulating tumour progression and metastatic spread ? Certainly this is a new approach which has only recently become available as a treatment for prostate cancer so the outcome of treatment has not been thoroughly studied. Early indications are that stimulating the immune system in the way that Provenge works could actually promote the mobilisation of tumour cells around the body and promote metastatic spread of the cancer to the bones.

Here are some recent review from patients who have tried Provenge

I was initially excited about the Provenge treatment and the concept of teaching my own immune system to destroy the cancer cells but the reality is very different. After the treatment I rapidly became disappointed as the cancer was spreading and destroying my bones causing a great deal of pain. I than was put on Zytiga Aberration and within two days my pain was all gone and my PSA went from 39 to 7. I am still here alive walking and talking. Jimmy


I am taking Zytiga and have not had chemo as required by FDA approval. I have already had Provenge which did not work. Zytiga has been a miracle, pain has been gone, PSA went from 39 to 7. I am sad to report that now my PSA is climbing. Just 1 point per month and is now at 9. Don't know. I am in a wait and see mode! I am going to hang on on to feeling good as long as I can. No side effects from Zytiga. I wish you the very best in whatever you do! Jimmy


I have been through the Provenge treatment. I was part of a study trying to determine if less than the approved dose was sufficient. I am not aware of which group(25%, 50%, or 100%) of the dose I received. The process is relatively straight forward--you go to a center where they use a machine to separate the white blood cells to send to Dendreon Labs(this was the most trying part of the treatment, as you have to sit without moving your arms for the entire process). Three days later the cells are returned to the infusion center to be administered. I felt no significant side effects. Thank goodness my wife attended the process, as it was amazing how often my nose would itch, and she would have to scratch it for me. I am not sure how effective it was, but in the months following the treatment my PSA rose considerably--they said it would rise some, but it rose from the teens to near 50 in two months. Also, when we did a bone scan, there was an increase in tumors. My oncologist started me on taxotere. After 7 cycles, the PSA began to rise, and I was adversely reacting to the treatment, so we stopped the taxotere and moved on to Zytiga. Zytiga has been easy and effective compared to the others--four pills each morning, no measurable side effects, and my energy has continued to improve. I am now at the eighth month of using Zytiga and the PSA readings dropped from 29 to 2+ the first month, and have gone down to just below 1 over the term. I am nervous, as the study suggested that around the 8th cycle is when the cancer finds a way around this treatment--we will see in two weeks when I have my next labs.
I hope this is of interest!!
Hudco

Ok so after reading these posts I am wondering if Provenge is causing the cancer to worsen or is it just normal progression. My husband has been approved by his Dr. now waiting to hear from insurance. At this time he is doing pretty well thanks to a new super food supplement we found called salvestrol platinum. I guess I am wondering if doing the Provenge will cause his cancer to become more active again. He has extensive bone mets and lymph node involvement.


No, I bowed out of trying for the Prostvac trials last summer, and opted for Provenge instead. I was able to get a "grant" to get Provenge virtually for free. I am convinced that the Provenge failed (subsequent tumors and bone mets--clear before Provenge-- don't give me much confidence the Provenge did anything worthwhile).

I am now on Taxotere chemotherapy in a last-ditch effort.

Friday 13 July 2012

Zytiga Launched in Brazil

Brazil Launch of Zytiga for metastatic prostate cancer


Zytiga has been launched in Brazil.
Foi no WTC Sheraton Hotel, em São Paulo-SP e teve a participação de Dras.
The launch took place in March 2012 at the Sheraton Hotel in Sao Paulo and was attended by Dr Eleni Efstathiou, professora assistente do Departamento de Oncologia Médica do Aparelho Genito-Urinário
do MD Anderson Cancer Center da Universidade do Texas-EUA e Cora Sternberg, oncologista clínica do Memorial Sloan – Kettering Cancer Center e chefe do Departamento de Oncologia Médica do Hospital São Camilo – Forlanini de Roma e professora adjunta da Universidade La Sapienza, de Roma-Itália.Eleni Efstathiou, assistant professor in the Department of Medical Oncology Genito-Urinary Apparatus of the MD Anderson Cancer Center, University of Texas-USA and Dr Cora Sternberg, clinical oncologist at Memorial Sloan - Kettering Cancer Center and chair of the Department of Medical Oncology, Hospital Saint Camillus - Forlanini of Rome and adjunct professor at the University La Sapienza, Rome, Italy. Eu e Dr. Ricardo Augusto éramos os dois únicos oncologistas clínicos presentes oriundos do Rio de Janeiro.
Dr. Ricardo Augusto and Dr Ricardo Teixeira were the oncologists attending from Rio de Janeiro.
Graças a esse novo medicamento tudo indica que estaremos transformando o câncer de próstata metastático em uma doença crônica e com sobrevida larga; trata-se do Acetato de Abiraterona, em forma oral, comprimido de 250 mg ea pauta diária é de 1000 mg ao dia; a sua indicação médica principal é na resistência e/ou progressão de doença neoplásica após o uso de Docetaxel; no frasco temos 120 comprimidos por isso deverá ser 1 frasco ao mês; combinado ao corticoide prednisona ou prednisolona, mais ainda nos casos clínicos resistentes à castração cirúrgica e/ou médica com medicamentos prévios como ciproterona, flutamida ou bicalutamida; é feito tomada única diária e não durante a refeição e deve ser pelo menos 2 horas depois de uma refeição, deglutidos inteiros e com água.
Thanks to this new drug it seems that we are transforming metastatic prostate cancer into a manageable chronic disease.
Zytiga is Abiraterone acetate in oral form, as a tablet of 250 mg and the dosage is 4 tablets (1000 mg) daily; its main medical indication is the resistance and / or progression of neoplastic disease after using Docetaxel.
There are 120 pills in a bottle which will last for one month. This is combined with the steroid prednisone or prednisolone.
O corticoide deve ser em dose baixa, 5 mg, duas vezes ao dia, sempre com proteção de mucosa gástrica por exemplo, com ranitidina.The steroid should be taken at a low dose, 5 mg twice daily. Antes de iniciar o Zytiga® deve ser realizado hepatograma e com controle mensal de suas enzimas hepáticas, monitorar também retenção líquida, pressão arterial e potassemia; Zytiga® não pode ser usado em hepatopatas crônicos; se no curso do tratamento houver aumento dessas enzimas hepáticas a dose de Zytiga® deve ser reduzida para 2 (dois) comprimidos ao dia com a normalização das enzimas.
Before starting the Zytiga ® should be performed a hepatogram and monitoring of liver enzymes, and also monitor fluid retention, blood pressure and potassium. Care should be increased in patients with hypertension, hypokalemia and fluid retention.
O tratamento com Zytiga® deve ser mantido até que ocorra a progressão dos níveis de PSA, combinado a progressão radiológica e sintomática ou clínica do câncer de próstata. Zytiga ® treatment should be continued until there is progression of PSA levels, combined with radiological progression and symptomatic or clinical prostate cancer.
Não se espera que Zytiga® afete a capacidade de dirigir viaturas ou de operar máquinas industriais.
Zytiga ® does not affect the ability to drive cars or operate machinery industry.
Recomenda-se cuidados se administrado com medicamentos ativados ou metabolizados pela CYP2D6 e não temos dados sobre a interação com álcool ou com nicotina.It is recommended that care is administered with drugs metabolized by CYP2D6.
Os paraefeitos mais frequentes são: edemas, queda do potássio no sangue, hipertensão e infecção urinária.The most common side effects are edema, decreased blood potassium (hypokalaemia), hypertension and urinary tract infection. It is manufactured and marketed by Janssen-Cilag, and has a very special niche and research show clinical cases with survival greater than 3 (three) years, so it is a major breakthrough in oncology.
As we said at the outset that with Zytiga we will be soon turning metastatic prostate cancer into a chronic manageable disease, not with a short survival but with extensive survival and quality of life.

Wednesday 11 July 2012

Zytiga Sales Soar

Zytiga sales have exceeded all expectations and is one of the fastest selling cancer therapies ever launched.

Comparing Zytiga and Provenge Sales Trends
$ millions 1Q, 2011 2Q, 2011 3Q, 2011 4Q, 2011 FY, 2011
Worldwide
Provenge 28 50 64 82 224
Zytiga 0 55 100 141 296
Total 28 105 164 223 520
US
Provenge 28 50 64 82 224
Zytiga 0 36 62 85 182
Total 28 85 126 167 406
Foreign
Provenge 0 0 0 0 0
Zytiga 0 19 38 56 114
Total 0 19 38 56 114

Latest sales figures for Zytiga showed that it had outsold its nearest rival Provenge in the first quater immediately following its Launch. Here Zytiga sales worldwide were $ 55 M whilst Provenge was $ 50 M. Sales of Zytiga have been increasing by over $ 10 M month by month culminating in a final quaterly sales figure of $ 141 M. The final 2011 sales of Zytiga was $ 296 M and sales for 2012 are projected to reach $ 1 Billion with quaterly sales set to exceed $ 250 M.