provenge

Packard,

We guys fighting in the main body of the engagement really appreciate the work of you advance scouts out there is the brush flanking and outmaneuvering the beast. We have it more and more on the run and you guys are a big part of the push.

49packard,

so excellent report! It really shows how immunotherapy is doing great job of fighting cancer.

On 25 June 2013 Charles G. Drake, MD, PhD, Associate Professor, Oncology, Immunology and Urology Johns Hopkins University School of Medicine share his understanding on the rationale for implementing immunotherapy in the treatment of prostate cancer with UROTODAY:

" that the idea behind immunotherapy is that the body’s own immune system can be enlisted with the goal of putting cancer into remission, to bring about actual shrinkage of tumor cells, or in the absence of that, have cancer stop growing, develop stable disease, or even just slow down the growth of disease. “That is the general concept, and there are a multitude of really good reasons why this makes sense. We have to remember that one of the reasons why cancer defeats us is that tumor cells evolve over time, and they retain the capability of adapting to pressures of the environment, particularly to agents such as chemotherapy. They develop new mutations, and, thus, ways to escape from most of our established treatments. The difference with immunotherapy is the immune system ‘understands’ that; the immune system was designed to respond to pathogens, which behave similarly. So, as the pathogens change their structure, or their molecular structure, the immune system can follow and hopefully get ‘ahead of the game.’That is why we think immunotherapy is an attractive approach to an evolving disease like cancer, and that is the rationale for recruiting the immune system, or immunotherapy, in the fight against cancer..."

Pepsiguy,

it is so good that your doctor could catch you so early and most important to offer Provenge and no convenient for doctors pills like Zytiga and so you could miss that narrow window of opportunity when you can benefit the most from this immunotherapy. Just two more infusions left for you and you are done with it ! Good lack on Monday and hope the SE of infusion will be less or none of first infusion.

From the same interview with Dr.Charles G. Drake:

" ..it turns out that if you look carefully, the patients who were earlier in their disease course are the ones who seem to have most benefit. By that I mean men who were asymptomatic, men who have less of a disease burden, men who have a lower PSA and so on. That is the current reality but if you take that to its logical extension, maybe we do not want to wait until the men are metastatic and castrate resistant to give immunotherapy, it might have a chance to work better in earlier disease stages...
In summary, in the current time immunotherapy is approved and we search for men who have early stage, metastatic castrate resistant disease. We honestly need to catch them as early as we can, at the first sign of metastasis in the metastatic castrate resistant patient.. "

PracticeUpdate just recantly posted videoreprint: "Lower Baseline prostate-specific antigen is associated with a greater overall survival benefit from Sipuleucel-T in the immunotherapy for prostate adenocarcinoma treatment (Impact Trial)". It is 4 parts video with Daniel J. George, MD Director, GU Oncology Duke Cancer Inctitute and Leonard G. Gomella, MD Chairman, Urology Jefferson Medical College. it is very informative and usefull who are interesting in Provenge :

www.videoreprints.com/

My best to all of you

Pepsiguy,

It is good that 2nd infusion was better tolerated then 1st and your SE no so bad!
It is should remember that the safety evaluation of PROVENGE is based on 601 prostate cancer patients in the PROVENGE group who underwent at least 1 leukapheresis procedure in four randomized, controlled clinical trials. The control was non-activated autologous peripheral blood mononuclear cells.
98.3% patients in the PROVENGE group and 96.0% patients in the control group reported SE. So it is nature of IV infusion. Glad that you finished it in normal time. It is very important to administer PROVENGE via intravenous infusion over a period of approximately 60 minutes.

Also from Provenge label:

"Acute infusion reactions such as chills, fatigue, fever, nausea, and joint ache were frequently observed in studies of PROVENGE. To mitigate such reactions, premedication, consisting of acetaminophen and an antihistamine such as diphenhydramine, was administered in clinical studies prior to infusion. In the event of an acute infusion reaction, the infusion maybe interrupted or slowed, depending on the severity of the reaction. Appropriate medical therapy should be
administered as needed. In controlled clinical trials, symptoms of acute infusion reactions were treated with acetaminophen, intravenous H1 and/or H2 blockers, and low dose intravenous meperidine.
If the infusion of PROVENGE must be interrupted, the infusion should not be resumed if the PROVENGE infusion bag will be held at room temperature for more than 3 hours."

dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=8309b497-5d4e-4408-ac0c-2452c11c8a35

One more to go! Good luck!

My best to you

Mattitude,

First welcome to HW and I think others members and moderators are joining with it.

So sorry to hear that your step dad has severe pain. It is difficult to say if this pain from SE of Provenge or other drugs or from his metastases. I think he contacted to his doctor and he has plan how your dad can manage it. I hope your step father will be able to finish his treatment with Provenge.


One more good news for PC patients in Europe.

At its June meeting, the Committee for Medicinal Products for Human Use (CHMP) gave positive opinions on Sipuleucel-T (Provenge). Assessments conducted by the CHMP are based on purely scientific criteria and determine whether or not the medicines concerned meet the necessary quality, safety and efficacy requirements. This recommendation will now be forwarded to the European Commission (EC), which will issue decision (it is take 60 days). Usually EC followed recommendation of CHMP.

"Sipuleucel-T has been shown in clinical trials to improve overall survival by 4.1 months, compared with placebo. As an immunotherapy, sipuleucel-T is considered to be less toxic than the therapies currently available for this indication, according to press materials from the CHMP. Therefore, the review panel concluded that the benefits of sipuleucel-T outweigh its risks, and recommended its marketing
authorization."

www.medscape.com/viewarticle/807077?src=wnl_edit_tpal&uac=195263EJ

Happy Independent Day!

My best to all of you

Todd,

It is hard to imagine that I'm down to one treatment left on Provenge. My Onc had put me back on Casodex at triple dose and it will be interesting to see where my psa is when I go back to see him later this month. He wanted to get me thru Provenge before going to anything else. If psa is up I may try Keto as he had said he had no problem trying that when something else was needed. I will know later this month.

Kurt

Kurt we are all pulling for your Provenge success.

Hi all in Provenge LAND:

You can look back on my postings to see it took six(6) months for my Provenge to turn around my PSA.

When I started Provenge my PSA was 9.26. It toped off at 141.0 3/19/13.

It  looks like the lower the PSA at the start the better it  works.

Today my PSA is 79.50.

Feel Great.   

President

Wheels for Prostate Cancer Research, Inc.

Fighting PROSTATE CANCER  With PROVENGE

www.WfPCR.org/

49Packard

Finished my third and final infusion on Monday. Now we will see if it pays off.

Thanks

Urotoday published on 05 August 2013:

"Immunotherapy in a mCRPC patient: The large urology group experience - Video Lecture

In this presentation, Dr. Christopher Pieczonka of Associated Medical Professionals discusses the treatment experience, in a large urology group setting, of patients receiving immunotherapy for metastatic castration-resistant prostate cancer (mCRPC).

Dr. Pieczonka is currently the executive vice-president of the Physician Teamster Alliance of CNY Local #1149 and has a specialty interest in the treatment of advanced prostate cancer. His patients were the first to be treated with Provenge® (sipuleucel-T), a new immunotherapy for metastatic prostate cancer.Purpose of this videolecture is increase educational awareness."

I would like highlight several important details from this video:

WHY IMMUNE THERAPY FIRST? on 12:46 min (Dr. C. Pieczonka use the same Figure that I talk in my previous post from 7/21/2013 )

- tumor biology rules: the faster growing tumors will lead to reduced survival...;

- immunotherapy may slow the tumor growth rate over time without leading to marked short-term tumor shrinkage that could lead to improved time to progression ( trajectory A in Fig 1 );

- on the contrary cytoreductive therapy causes a transient effect on tumor grows rates ( trajectory B in Fig 1);

- this suggest that the most prudent use of immunotherapy would be early in the disease process. This would allow sufficient time for any potential effect on tumor growth and can produce a synergistic effect ( trajectory C ).


QUARTILE DATA:

- Provenge treatment effect appeared greater with decreasing baseline PSA:

</=22 PSA - median survival- 13 months; the OS hazard ratio- 0.51;

- Estimated 3-year survival in the lowest PSA quartile was 62.6 % for Provenge patients and 41.6 % for control group, representing a 50 % relative increase.


Dr. C. Pieczonka talk about they own data, that showed similar trend. It is important to put on Provenge early as possible .


SO HOW DOES THE IMMUNOTHERAPY HELP THIS TREND SEEN IN MEDIAN SURVIVAL?

IMMUNE RESPONSE THEORY:


-The immune response may also target antigens not specified to certain vaccine. with tumor necrosis, there can be release of other antigens from heterogeneos prostate cancer lesions through the process called by " self- or auto-vaccination";

-the secondary antigens can be processed by immune system through immunomodulation action of ex-vivo uploaded vaccine such Provenge with possible guidance to kill cancer cells;

-these "new cancer antigens" are a product of both mutations and amplifications of androgen receptors that facilitate signaling process in castration level enrollment.


WHY IS THIS IMPORTANT?

- Provenge had rough acceptance ( My take: snake oil? no biomarkers? negative bias in media? war against Provenge? Huber false theory? big money involve? See my previous posts )

- most of this has been criticism of only 4 months (My take: crossover effect, 64 % from placebo group choose frozen Provenge, adjusted model showed almost 8 months OS without crossover, abstract #144 ASCO 2012, Provenge ONLY DRUG that showed stat. sign. OS in PRECHEMO space. See my previous posts );

- our own clinical experience has shown that we identifying patients much earlier in the disease course then those we treated in the pivotal study ( Impact);

- based on the quartile data we would expect much better OS on these patients;

- what's next? Combination/ Sequencing trials.

TAKE HOME MESSAGES:

- screen for metastasis with Na/F scan ( if possible);

-there is no current biomarker available to monitor treatment response with Provenge;

- the quartile data can be used to counsel patients about OS,
lower PSA appears to be better;

- the combination of Provenge with other types of cytoreductive therapy and immuno-modulators may lead to synergestically enhanced immune response;

- further clinical trials using combinatorial approach defining optimal sequence time and doses of these piplines is needed.


www.urotoday.com/Prostate-Cancer-Immunotherapy/immunotherapy-in-a-mcrpc-patient-the-large-urology-group-experience-video-lecture-by-christopher-m-pieczonka-md.html

Post Edited (HOPENEVERDIE) : 8/21/2013 11:53:57 AM (GMT-6)

Hi Preacher Man -

You shared experiences with your dad as we both shared what our fathers are going through. I am very curious about the question you raise here. My dad has been experiencing the same thing but is much earlier on in the post Provenge process for him. His PSA was 16 in May and started Provenge later that month. He completed the treatment in early July and his PSA was then 36 and is now 60 from his last visit to the doctor this past Tuesday. I don't know if I can say the fact that it went from 36 to 60 vs. 36 to 72 could be considered progress in reducing the doubling time at this point?

He just started Zytiga about two weeks ago. His oncologist is not concerned about the doubling and said he expected this. My dad also expected this (he is a scientist and does a ton of research).

We are waiting for the first PSA test post Zytiga - Doctor doesn't expect it to drop much since it has been a short time but will see.

I just feel like there is a whole fuzzy area about Provenge that we don't know about what to expect, if we can expect anything - good, bad or indifferent. I know it is not supposed to lower the PSA. I appreciate that the gentleman named Packard has shared his successful Provenge experience - just wonder if anyone out there has any input on this as well.

Biggest challenge for my dad is getting the spinal fractures to heal - he is trying to stay active but is also laying low with this. Says he's starting to feel better now that he's on Zytiga -is tolerating it very well. Doctor says have to just let it heal - really nothing to do, prescribed pain meds as needed. Just a bit frustrating.

My father:
Dx 2001 - RP - cancer confined to prostate
Radiation post RP as precautionary
Lupron and Casodex therapy for years following - no issues
September 2012 - PSA 5 - hormone therapy, no issues
May 2013 - PSA 16, scans revealed bone mets on the spine
May 2013 - Lupron injection
May 2013 - July 2013 - Provenge
July 2013 PSA - 36
August 2013 - MRI and scans due to back pain -showed a couple of small spinal fractures -one in middle of back causing back pain - doctor things osteoporosis related but there is a bone met there - no tumors. He had some issues with back off and on over the years -nothing severe but it could hurt or give out if too much overexertion. He is very fit.

August 2013 -started Zytiga, PSA prior to Zytiga was at 60. Also given injection of Xgeva

CMA,
Dad did really well on Zytiga. I think the steriod also benefited him more than we realized. We his next appointment on Wednesday and fully expect Xtandi to be proposed. His Dr stated at the last visit that his concern was the PSA going beyond 30 due to all the meds etc. the clear scan was great but the Dr really thinks visible progression is close.

We are also beginning to notice huge mood swings and mental struggles with things that should be normal. He is tired though he rountinely works out with weights and bike. Stamina though is dropping.

Our concerns with the Xtandi are the fatigue that seems to hit everyone on it. He is not wanting any QOL change from meds and none of us like the idea of Jevtana. Dieing well beats dieing med sick in our book.

Going to be an interesting few days for us as we walk this path while trying to learn all we can to make wise decisions.

Preacher Man -

Greatly appreciate the feedback on Zytiga. I'm hoping. Read the latest about your dad and will keep him in my prayers. Hoping you find a happy medium for him. I agree with you about Zytiga - seems like there is repeated feedback of positive results from many on this forum with it. I only wish it could work permanently. Sounds like it stops being effective after several months -to a year -wonder why that is. Haven't really seen anyone share they've been on it for longer than that.

As for Provenge -I am leery as well but the fact that your dad's scans are clear of new activity are maybe a sign that it worked - that it was the booster underneath the Zytiga -supposedly Provenge helps the body respond well to other medications. What was his PSA at the time of Provenge? My dad has not had PC in lymph nodes thus far. You mentioned behavior was changing -has brain been checked/scanned? Have you sought out somewhere like a MD Anderson or Sloan Kettering, etc. for additional advice on what drugs next?

Hoping your family gets some options everyone feels comfortable with.

Take care!
CMA

PreacherMan12,

What is sad, that no only you or many PC patients but some doctors think that Provenge doesn't work and use Media and other unscientific sources ( for example financial situation ) for justifying their believes. Some prominent doctors like Dr. D. Petrylak said so many doctors come to him and use reason not to use Provenge like "Huber false theory", it is concern him and shame and unfortunately that this paper was even excepted.

It is unacceptable. What is acceptable - scientific evidence !

True - Provenge showed overall survival (OS). The only drug in PreCHEMO space that prolong survivor. No one drug, no Zytiga, no HT, no Xtandi yet showed OS in this space. ONLY PROVENGE.

Everybody expect miracle from Provenge and when it didn't happened that conclusion- Provenge does not work. No body expect miracle from Zytiga, Chemo, Xtandi and other drugs.

You said your father benefit from Zytiga. It is wonderfull ! But remember many patients didn't response to Zytiga too. You can read about it on this website or others. For example:

" David Lawrence, on August 27, 2013 at 11:30 am said:
Interesting stuff.I followed docetaxel with abiraterone and prednisolone. My PSA lept to 500+ ng/ml. I then came off everything for a couple of months, and my PSA came down to 28 ng/ml. I then moved to enzalutamide + prednisolone and over the last 6 months my PSA has crept up to 220 ng/ml again. My doctors are talking about putting me back on docetaxel!
It’s a confusing life. … By the way, I have refused to go back to docetaxel. … I am not going to suffer that loss of quality of life again."

It was patient response to the article about cross-resistance between Zytiga and Xtandi. It is why many doctors recommend to use sequences of drugs with different MOA.

prostatecancerinfolink.net/2013/08/26/abiraterone-acetate-or-enzalutamide-first-it-seems-to-matter-for-some-patients/#comments

So many patients who use Provenge also benefit from it .

Remember no biomarkers yet for immunotherapy, old biomarkers ( as PSA) don't work.

Don't forget all patients are mHRPC. It means median life expectancy for them 36 months.

Goal - EXTEND LIFE and QOL.

It is no easy to show OS for drugs in HRPC.

PC patients was lucky to have so many new drugs in last 3 years. We don't now how often other new drugs will come.

Remember just recently Takeda announces unbinding of Phase 3 Study of TAK-700 in mHRPC patients after Chemo because TAK-700 would likely not meet the primary endpoint of improved OS. It will be even more difficult for them show OS in prechemo setting .


But come beck to Provenge. You said "I struggle to find more than a few who have actually seen real success."

So many of them on this MB, I posted several links, you can read about them on company's website and on Provenge's website.

You said " Yes my father feels better, but if no effect is evident from the cancer itself I find it hard to think of it as making a major impact."

Remember no biomarkers yet for immunotherapy, old biomarkers ( as PSA) don't work.

You said "... The Dr and I think the good scan report is more the benefit of the 14 months on Zytiga than the Provenge"

Your father 9 months after Provenge treatment and the inhibitory effect keeps accumulating over time. So I belive it can contribute to Provenge.
PROVENGE treat cancer, other drugs like ZYTIGA, Xtandi treat symptoms (PSA redaction?). Other therapies have a benefit that disappears when the therapy stops but that Provenge will remain in patients body for an extremely long time, maybe the rest of their lives.

And about repeated information: In my country where I am from, we have proverb "Repetition is the mother of knowledge."

So I repeat again:

"Dr. Freedland compared this to a runaway train going over a broken bridge, i.e. immunotherapy is going to slow this train down, but it is never going to stop the train or reverse the train. Therefore, the earlier you treat with immunotherapy, the better it is...treat aggressively to get as many agents in as
possible..."

It is sad that patients need to be mHRPC to receive Provenge. Who knows maybe we can cure or make it chronic decease if give early. Right Devasted1 ?

Sometimes FDA approve drug without result from trial like this:" On July 20, 2012, the U.S. Food and Drug Administration (FDA) granted accelerated approval of Kyprolis® (carfilzomib) for Injection for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent (IMiD), and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval was based on response rate.
Clinical benefit, such as improvement in survival or symptoms, has not been verified."


Immunotherapy and special when it personalize for each patients like Provenge is future for cancer.

It is why vaccine immunotherapies are being tested in more than 600 clinical trials as treatments for many of the cancers . Just 2 days ago on 08/26/2013 AstraZeneca took a further step to bolster its pipeline of new cancer drugs Monday by agreeing to acquire privately held U.S. biotech company Amplimmune. It's product line-up includes AMP-514, an anti-programmed cell death 1, or PD-1, medicine that is expected to ready for testing in patients later this year. So big farma know what a gem is immunotherapy.

But it is also no easy. A lot of them fail. The closest immunotherapy to Provenge: Yervoy ( result could be known 2015) and Prostvac ( maybe 2016). We don't know if they are successful or if successful they will be better then Provenge.

And last you said "...there financial situation is a disaster about to occur".

It is difficult to tell why only 3 000 patients last year were treated with Provenge and maybe the same number this year. about 60 000 HRPC patients diagnose every year and if even 50 % of them refuse to take Provenge ( they don't believe like you or doctors don't believe , or they progress so quick that no reason give them it, even when majority of patients with mCRPC will be asymptomatic when initially diagnosed ) it is still 30 000 that could benefit from this treatment.
Is some "Forces" interesting to make company to go in the bankruptcy and put this drug on the shelf ? or maybe management ( new CEO and his team come to company just 2 years ago) of company interesting take it private, so they need sabotage sell of this drug ? Why so many drama around Provenge? I don't know answer. Who behind of it ? WHO bring this new team to the company? Where PCF with all its money and no words from them about this treatment and no effort to educate patients ? Are Milken and his friends behind those "Forces" to destroy Provenge and they are busy to fill up they pockets then save patients ?

Here my opportunity to say my BIG THANKS to Malecare Prostate Cancer Support , personal Joel T. Nowak, Malecare’s Director of Advocacy and others who try to educate PC patients about Provenge .

advancedprostatecancer.net/

Bottom line is "...on the other hand, you treat a population of men in this way and they live longer than the population of men not treated in this way... "( Dr. O. Sartor, you can read his opinion about Provenge in my post 2/4/2013 ).

And last the most important is your father had Provenge and will no look back for missed opportunity like thousands other patients. And when he move to other drugs and respond to them or just continue to live his life think about that maybe Provenge that still inside him is working every day and every hours probably for the rest of his life.

My best to you and your father

" I have learned that there are things in this world that I can not change, but I can embrace them and accept them as they make up who I am." (Joel T. Nowak}

Post Edited (HOPENEVERDIE) : 8/29/2013 6:02:00 AM (GMT-6)