provenge

JerryL,

At first I am sorry for my misspelling Dr. Myers' name, special if it offended you personal and I fixed it right away, of course you found a lot spelling and grammatical mistakes through all my posts and thank you for no been sarcastic about them. You can see that English is not my first language and it is always leaning process for me ( I speak 4 languages and 3 of them no perfect but I think if I posted in my native language I will not have this problem). Thank you for correction and understanding.

Second you maybe noticed when I am posting I am trying to post facts and provide link to them. So when I posted names of doctors who supported Provenge I used them in my previous posts. I rechecked and found next about Dr. Myers that he talk on his blog ASK DR MYERS :

10/17/2012-Combining PC Drugs: about using 3-4 anticancer drugs in combination. This prevents the cancer from mutating to escape the treatment. The drugs need to be of different families in other words, three different anti-androgens can't do it, but drugs from different families (chemo, an anti-androgen, and Provenge) might. He's saying that now that there are multiple options with manageable side effects it's time for more investigation of combination therapies.

07/07/2010- Dr. Myers talks about a patient who'd been on a Provenge trial, after patient received Taxotere Dr.Myers put him on Estradial + Ketoconazol + Lukein.it is the best response that he'd ever seen( on Estradial + Ketoconazol + Lukein). He suggest that maybe pretreated with Provenge create better effectiveness for Estradial + Ketoconazol + Lukein and bringing immune system works in more effective way.
So maybe this case gave us clue how sequence drugs , Dr. Myers thinks.

07/20/2011-Bone Metastases and PC: talk about Provenge;

05/26/2010-More on Provenge: cocktail" different immunotherapies", very interesting time for immunotherapy, talk about starting Provenge early, Hormone therapy and after Provenge;

05/18/2010- Provenge: talk about crossover in trail, his guess real OS will be more then 4 months, talk about cost for Provenge and compare to Taxotere is about the same cost( 10-12000$ for month of Taxotere with treating SE, different tests, support stuff). Prefer Provenge over Taxotere.

askdrmyers.wordpress.com/

Dr. Myers is an extraordinary researcher and he uses different kind of “cocktails” in the treatment of advanced prostate cancer and see future for " cure" PC in such kind of treatment, so my expression that he is seeing immunotherapy as one of the part of it.

I know how important to post facts about any medical treatment and provide prove to them. When I started to read on HW a lot men thought Provenge is like "snake oil" and some men even mention their doctors think the same way. It is a lot misinformation about Provenge still in the Media. But unfortunately many men lose their life without even try these treatment and maybe they could be benefit from it.
I've heard over and over that doctors said it's too much money for too little time.
Patients ARE going to depend on their docs for appropriate treatment. If I have to tell my doctor how to treat me - I need a new doc in my opinion.

When I was going through my bookmarks on my computer I found interesting article about Provenge , how this treatment come to patients.I saved it 5 years ago. It is from 2007. Maybe it will be interesting for you to read:

www.lawyersandsettlements.com/articles/drugs-medical/provenge-01635.html#.UWBX2ldULMU part 1


www.lawyersandsettlements.com/articles/drugs-medical/provenge-appeal-01644.html#.UWBYd1dULMU part 2

I would like to repeat Dr. SCHOLZ words again:

"... if I am asked a slightly different question—“What type of new technology has the greatest potential for saving lives?”—my answer will always be the same for every patient: Immune therapy...
there is one intrinsic capacity in our bodies that successfully parries millions of different attacks on our health: the immune system. Therefore, if a cure for the myriad of different cancer types exists, it will probably result from successfully harnessing this incredible system...
The good news is that a properly directed immune system can and will eradicate cancer...
Double-blind, placebo-controlled trials show Provenge slows cancer progression and prolongs survival just as well or even better than other standard treatments such as chemotherapy or second-line hormonal therapy.
People forget that even though Provenge is administered over a six-week period, once the immune system is activated, it keeps functioning indefinitely; it’s the gift that keeps giving for the rest of your life. Therefore, even if Provenge only slows disease growth slightly, the inhibitory effect keeps accumulating over time. So over a period of years, even a mild effect can become substantial...
its pattern of improved survival with earlier stage disease seems to fit the hypothesis that the inhibitory effect of Provenge results in a progressively longer survival when its effects are allowed to accumulate over a longer lifespan. Based on this data one would logically conclude that Provenge induces the biggest benefits when administered at the earliest possible stage."

My best to you.

Post Edited (HOPENEVERDIE) : 4/8/2013 2:05:45 PM (GMT-6)

Regarding early use of Provenge, this was published Friday:

Dr. Crawford on Sipuleucel-T in Advanced Prostate Cancer
E. David Crawford, MD
Published Online: Friday, April 5, 2013

E. David Crawford, MD, professor in Surgery and Radiation Oncology and the head of Urologic Oncology at the University of Colorado, Anschutz Medical Campus, discusses the effectiveness of the immunotherapy sipuleucel-T (Provenge) as a treatment for men with advanced prostate cancer.

Overall, Crawford notes, sipuleucel-T is an effective agent that extends life with minimal side effects. This agent was approved based on a 4.1-month median improvement in overall survival (OS), as observed in the phase III IMPACT trial. In a more thorough examination of this trial, subgroups of patients were identified who were more likely to benefit from treatment.

In the subgroup analysis, patients with PSA levels lower than 21 with few bone lesions experienced a significant prolongation in OS from 4.1 months to approximately 18, Crawford notes. This data reflects the fact that immunotherapy tends to work better earlier in the disease, Crawford states.

http://www.onclive.com/onclive-tv/Dr-Crawford-on-Sipuleucel-T-in-Advanced-Prostate-Cancer

Hope,

I am not offended at all. I just wanted to make sure we were talking about the same doctor.

I don't know of one patient that Myers has prescribed Provenge. Again, I am a fan of Provenge, but I don't think Myers is. If you know of any of his patients that have been prescribed Provenge, please let me know. I'd like to talk to them.

Thanks for all the info....and I am impressed that you can speak multiple languages. I have problems with just one.

Jerry

I have heard from Dr. Crawford...he's preparing a paper now for presentation at a soon-to-be-held conference. His work is embargoed for the time being, so we'll just have to wait for the details.

Sun

Jerry L,

My understanding that Doctor who prescribes Provenge also provides this treatment in his office. It is require several steps: work with insurance about payment; doctor pays to Dendreon for Provenge ( 31000$ for each infusion,); administration of this drug ( nurses should be trained how handle and infuse ), again work with insurance that to be certain it paid to company for treatment in order for doctor to receive his money back. . It is a big commitment that everything should be done in time ( shelf life for Provenge is just 18 hours from moment its was manufacturing individual for each patient) .
It is very different from just prescribing pills, for example like Zytiga, Xtandi.

Recently on Onclive was discussion about it:

"Reimbursement Issues in Prostate Cancer, Part I
Peer Exchange
Published Online: Friday, February 1, 2013

Raoul Concepcion, MD, FACS, begins the conversation by noting that urology as a business faces reimbursement and operational challenges.

Steve Dobbs, FACHE, says that his practice’s latest reimbursement issue has been with sipuleucel-T (Provenge), which is an expensive drug. According to Dobbs, the process to guarantee reimbursement is complicated. Initially, Dendreon completes the verification of benefits and the practice does a secondary review. Throughout the process, nurses are in contact with patients to notify them of any co-pay issues.

Administering sipuleucel-T has become such a large financial commitment, Dobbs says, that it’s now a separate line item in monthly board meetings.
With regards to LHRH treatments, such as leuprorelin (Lupron), Dobbs’ practice reviews the reimbursement process on a quarterly basis.

The question many urologists face now is selecting the most appropriate treatment as new costly therapies gain approval. To solve this problem, medical experts discuss the clinical side of administering new drugs, while operations committees decides which agents to carry, and management teams negotiate costs and GPO relationship issues."

www.onclive.com/peer-exchange/prostate-cancer-management/Reimbursement-Issues-in-Prostate-Cancer-Part-I

I would like to notice that now reimbursement for doctors less then 30 days , but it is still big commitment for them because Provenge is Personal Medicine, altered for each individual patient.

Post Edited (HOPENEVERDIE) : 4/10/2013 12:28:21 PM (GMT-6)

Adjust,

Contact the Dendreon Hotline for help. In particular, ask to speak with Jenifer Lill, if she's available. She's the woman who assisted Todd Seals.

Call 1-800-667-5924

Sun

Two upcoming AUA presentations/papers with Dr. Crawford as an author

http://www.aua2013.org/abstracts/search.cfm

Search under Crawford, E. David


Sunday, May 05, 2013 03:30 PM-05:30 PM
Prostate Cancer: Advanced (I)
Podium
Ferring Pharmaceuticals
716: Analysis of disease control-related outcomes from six comparative randomised clinical trials of degarelix versus luteinising hormone-releasing hormone agonists
Neal Shore; Kurt Miller; Bertrand Tombal; E. David Crawford; Cathrina Karup; Egbert van der Meulen; Bo-Eric Persson

Monday, May 06, 2013 10:30 AM-12:30 PM
Prostate Cancer: Advanced (III)
Moderated Poster
Dendreon
960: Optimal timing for treatment of metastatic castration-resistant prostate cancer (mCRPC): sequencing and identifying parameters of early progression with sipuleucel-T
E. David Crawford; Adam Kibel; Neal Shore

Tuesday, April 9, 2013
A New Immune Treatment Combination (part ll)
BY MARK SCHOLZ, MD

"In my last blog I contended that of all the different ways to treat cancer—hormone therapy, chemotherapy, radiation or surgery for example—immune therapy has the greatest potential to save lives: Only the immune system, by its very nature, has the ability to adapt to the many thousands of varieties of cancer. Also, new breakthroughs in understanding how it works have led to real progress inharnessing the immune system to fight cancer.

One discovery—that the immune system uses a specific type of immune cell called the “dendritic cell” to detect cancercells—led researchers at a company called Dendreon to develop a five-step process for enhancing dendritic cell function...

Provenge partially circumvents this problem by activating the dendritic cells outside the body in the lab. But the dendritic cells still face a hostile inhibitory environment after they are re-infused. The question arises, “Wouldn’t Provenge work even better if the immune environment in the cancer patient could be rendered more “friendly"?”

...Yervoy enhances immune function by counteracting the excess amounts of suppressive hormones being released by the cancer...

Provenge and Yervoy used together are so attractive conceptually that the only question remaining is about the optimal method of delivery. Yervoy, unlike Provenge, can have serious side effects. In excess amounts it can induce the immune system to run wild and start attacking the organs in the body like the liver, thyroid and intestines. Caution dictates beginning with a small initial dosage of Yervoy.

In the study we will be conducting at Prostate Oncology Specialists in Marina del Rey the first three patients we treat will be given one-twelfth of a normal dose of Yervoy one week after the Provenge is completed. The second group of three patients will receive a one-sixth dose of Yervoy. The third group of three patients will get three-twelfths of a Yervoy dose. All patients will receive full-dose Provenge and will be closely monitored for disease response, immune function and for possible side effects.

Provenge and Yervoy are just two of the many exciting new methods being studied for harnessing the immune system to fight cancer. However, to my knowledge, we at Prostate Oncology Specialists are privileged to be the first to test the effectiveness of these two exciting treatments in combination. Our first patient is scheduled to start on trial this month.

www.prostatesnatchers.blogspot.com/

Has everyone seen these new Web sites? They might answer some questions you've had.

fightcancerwithimmunotherapy.com
www.fightcancerwithimmunotherapy.com/

Sun

Lower PSA linked to greater survival with sipuleucel-T in prostate cancer
By Sally Robertson, medwirenews Reporter
17 April 2013
Urology 2013; Advance online publication

medwireNews: Sipuleucel-T treatment may be of the most benefit to patients with metastatic castration-resistant prostate cancer (mCRPC) who have low prostate specific antigen (PSA) levels, say US
researchers.

An analysis of findings from the phase III Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) trial showed that the magnitude of treatment benefit was greatest in patients with better baseline prognostic factors, particularly those with lower baseline PSA values.

"These findings provide a rationale for immunotherapy as an early step in sequencing treatment algorithms for mCRPC and also suggest a greater benefit when immunotherapy is used earlier in the treatment paradigm," say Philip Kantoff (Harvard Medical School, Boston, Massachusetts) and team.

For the randomized, double-blind, controlled multicenter trial, which included 512 men with mCRPC, subgroup analyses were performed based on prognostic variables that have previously been used to predict survival in patients with mCRPC. These included serum lactate dehydrogenase, PSA, serum alkaline phosphatase, Gleason score, Eastern Cooperative Oncology Group performance status, hemoglobin, and the presence of visceral disease.

Multivariate analysis showed that of all the factors assessed, PSA was the strongest baseline prognostic factor for survival among the men, report Kantoff et al.

Furthermore, there was a significantly greater treatment effect with decreasing baseline PSA level such that those in the lowest PSA quartile (<22.1 ng/mL) had a 49% reduction in risk for death compared with patients in the control group, while those in the highest quartile had a 16% reduction in risk.

Furthermore, those in the lowest versus highest baseline PSA quartile had an estimated median survival time of 41.3 versus 18.4 months in the sipuleucel-T group and 28.3 versus 15.6 months in the control group. And the estimated 3-year survival in the lowest PSA quartile was 62.2% in the sipuleucel-T group, compared with 41.6% in the control group, a significant relative increase of 50%.

"The overall finding of a greater sipuleucel-T treatment effect in patients with generally more favorable prognostic features is consistent with the proposed mechanism of action of sipuleucel-T," remark the researchers. "Patients with a lower cancer burden tend to experience less immunosuppression systemically and in the tumor microenvironment."

"Therefore, patients earlier in the natural history of the disease would be anticipated to have a more robust and effective immunologic response to sipuleucel-T treatment," note Kantoff and colleagues.

www.medwirenews.com/1690/104214/Andrology/Lower_PSA_linked_to_greater_survival_with_sipuleucel-T_in_prostate_cancer.html]

SES AUA 2013: Session Highlights - Management of castration resistant prostate cancer (CRPC): Update of new treatments
Published on 04-02-2013

"Dr. Freedland went on to discuss treatment options for men with metastatic CRPC (mCRPC). He showed the well-known slide of the natural progression of prostate cancer and where different treatment options fit in (see below). When discussing this, he stated that the challenge is that there are too many treatment options, so the question is which treatment works best for which patient, and how do you get as many treatments in as possible for each patient, and in what sequencing?

Dr. Freedland explained that the median survival for men with mCRPC is about 24 months and there are now six treatments that have shown to prolong survival:

sipuleucel-T: 4.1 months
docetaxel: 2.9 months
cabazitaxel: 2.4 months
abiraterone: 3.9 months (post-chemo)
abiraterone: ??? months (pre-chemo, median OS not reached)
radium-223: 2.8 months
enzalutamide: 4.8 month

Following this, Dr. Freedland discussed sequencing of these available treatments and how to use them pre-chemo vs. post-chemo. For pre-chemo patients, sipuleucel-T and abiraterone are approved and available. For post-chemo patients, abiraterone, cabazitaxel and enzalutamide are available and approved, while a positive study with radium-223 is awaiting approval.

Dr. Freedland started to describe the available treatments for pre-chemo patients and he began with the only available immunotherapy for prostate cancer, sipuleucel-T. He explained that sipuleucel-T is a patient-specific therapy where they go through a three-course treatment, with each treatment two weeks apart. The patient comes in on day 1 for leaukapheresis, and on day 2-3 sipuleucel-T is manufactured from the patient’s own blood cells at Dendreon, and on day 3-4 they receive the finished immunotherapy product to be infused back into the patient. This process is done for three cycles over 3-4 days each time. The slide below shows a simplified overview of the sipuleucel-T process, starting with collection of the patient’s own blood via manufacturing at Dendreon and the finished product back to the patient.

There have been a few studies conducted that led to the approval of sipuleucel-T and Dr. Freedland discussed the randomized phase III IMPACT trial (IMmunotherapy Prostate AdenoCarcinoma Treatment) by Kantoff et al.. (NEJM 2010). This study included 512 patients with early stage disease, asymptomatic, or minimally symptomatic mCRPC, and the patients were randomized 2:1 into either sipuleucel-T or placebo and then followed to progression. After progression, the sipuleucel-T patients where treated at the discretion of the physician while the placebo patients either were treated at the discretion of the physician and/or received a “frozen” version of sipuleucel-T. The primary endpoint was overall survival (OS), and the secondary endpoint was time to objective disease progression. The study demonstrated an average survival benefit of 4.1 months in the sipuleucel-T group compared to placebo, which equals a 22% reduction in risk of death (all cause death). A post-hoc exploratory analysis showed that among men with the lowest quartile of PSA, i.e., men with the lowest tumor burden, sipuleucel-T improved median OS with 13 months while the men with the highest quartile of PSA had only a < 2 month improved median OS with sipuleucel-T.

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...

Scan early and often to detect metastasis and treat aggressively to get as many agents in as
possible...

Need to sort out sequencing and combinations

Dr. Freedland ended by saying that the future of CRPC looks less dark, and we are very slowly turning it from a fatal disease to a chronic disease.


Presented by Stephen J. Freedland, MD at the 77th Annual Meeting of the Southeastern Section of the AUA - March 14 - 17, 2013 - Colonial Williamsburg Lodge - Williamsburg, VA USA"

Stephen J. Freedland, MD, Associate Professor of Surgery Associate Professor in Pathology, Duke Cancer Inctitute

www.urotoday.com/Treatment-of-mCRPC/ses-aua-2013-session-highlights-management-of-castration-resistant-prostate-cancer-crpc-update-of-new-treatments.html?acm=28555_766&utm_campaign=trending-this-week-on-urotoday-040913&utm_medium=email&utm_source=newsletter_766

www.kezi.com/treatment-helps-prostate-ca.../

Tim's picture is the first one you seen when logging on to DNDN Web site. You might find his 3 year PSA graph interesting. It shows a double dip in PSA to near zero. I presume the first dip was after surgery but am puzzled by the second post-Provenge drop. We know he had hormonal and radiation therapy after surgery, and we also know Provenge was given in early 2012 according to the DNDN Web site. The local TV reporter mentioned that he is currently enrolled in trial as well. His chart looks almost exactly like how you might imagine a Xtandi plus Provenge chart to look based on what little we know about this potential combo. Of course, it is also quite possible the 2nd PSA drop came about because the trial he enrolled in actually added radiation into the treatment regimen, which may explain the sudden flurry of Provenge+Radiation combos trials being registered on the FDA[s Clinical Trial Web site since the 1st week of March 2013.

 

We know that he took Provenge in early 2012 and we look at his chart we see his PSA readout was still very low at that time. The question is: what did he receive in December 2012. Xtandi? No matter how stellar results are derived at least we know Provenge was part of the success formula.

If you freeze the video at the 50 second mark you will be able to study the PSA chart at your leisure.”