provenge

Great news all around.

 

HopenEVERDIE

Thank You .

I know everbody is getting sick of me talking about how good I feel.

But after putting up with all those side effect for 7 years this feeling needs to be told.

Will do a new PET scan before JUNE. 

49 Packard

living1963

Thanks for the comeback. It is great to be able to talk to someone that has done the walk.

Had my Lupron shot Friday and it is now 5 days later and I know it is working.

Lost my night errections altogether. Nose is running. And feel a little low today.

Shoot me an e-mail at [email protected].

49 Packard

Urology
Volume 81, Issue 2, February 2013, Pages 381–383

"Complete Biochemical (Prostate-specific Antigen) Response to Sipuleucel-T With Enzalutamide in Castration-resistant Prostate Cancer: A Case Report With Implications for Future Research

Julie N. Graffa, b, Corresponding author contact information, E-mail the corresponding author,
Charles G. Drake c, d, e, Tomasz M. Beer b

a Portland Veterans Affairs Medical Center, Portland, OR
b Knight Cancer Institute, Oregon Health and Science University, Portland, OR
c Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,MD
d Department of Urology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD
e Department of Immunology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,M

Objective

To describe the case of a patient with castration-resistant, metastatic prostate cancer who achieved a complete and durable biochemical response after treatment with sipuleucel-T while continuing with enzalutamide and to explore the immunologic basis for such a response.
Materials and Methods

We obtained serial prostate-specific antigen (PSA) measurements and bone scans to assess the patient's response to enzalutamide followed by the addition of sipuleucel-T. Using preclinical and clinical data, we describe his response through known immunobiologic mechanisms.
Results

This patient's PSA level became undetectable during treatment with enzalutamide and began to increase again after 14 months. He opted for treatment with sipuleucel-T, while continuing with the enzalutamide. This resulted in another complete PSA response 6 months after exposure to sipuleucel-T.
Conclusion

Sipuleucel-T typically does not produce significant PSA reductions, and, to the best of our knowledge, only 1 previous report of a durable complete PSA response in a patient with metastatic disease has been published. The timing of this response supports an immune mechanism. The biologic rationale for the combination, coupled with the clinical result observed in our patient, provides a basis for studies of the combination of sipuleucel-T and enzalutamide.

Figures and tables from this article "

www.sciencedirect.com/science/article/pii/S0090429512013441

It is important look at the FIGURE.

This patient was dx in 1997 with adenocarcinoma of prostate at age 54. Patient had a radical prostectomy. Diagnosed with gleason 3+5 and osseous metastases in 2002 and started Casodex. Patient was started on LHRH after disease progressed in 2007. In 2008 patient entered a P1 MDV3100 trial for patients who are Castration-Resistant (Hormone-Refractory) Prostate Cancer.
Provenge was started when PSA rose to 1.49ng/ml on 8-30-10. The cd54 count (which is a measurement of antigen upregulation) presenting cell jumped up to 23.6 fold on the 3rd dose of Provenge on 9-27-10. The median was 10.6 fold so this 3rd dose had a very strong antigenic effect. Also the PSA lowering effect took took several months after Provenge was given which is typical of vaccines. Enzalutamide has a quick PSA lowering effect but Provenge normally doesn''t so this is a very nice surprise.

"To the best of our knowledge this is the 1st report of these 2 agents administered concurrently".

MDVN currently has 800 patients on enzalutamide (+ 800 on placebo arm) in a prechemo P3. For those patients whose PSA progress and have to drop out of the trial they have the option of staying on Enzalutamide even if they decide to try another drug. Some will add Provenge. This trial reports 2H13 so it will be interesting to see how this small sub-group did on the combo tx.
Again, not stats, but look at the chart.
It sure is intriguing from a science point of view and it fits well with the theory that the combination of Hormone deprivation and PV may offer better outcomes than either alone. Additionally it fits even better with the theory that Xtandi, may be uniquely synergistic with PV because of their mechanisms of
actions.

I look forward to see the Data of Xtandi in a prechemo P3. Its trail should show OS for drug to be approved by FDA in PRECHEMO.
Remember Zytiga trial3 in PRECHEMO? The longest period of known median overall survival after a man is clearly metastatic and castration resistant is 3 years — among men who are asymptomatic or mildly symptomatic at initiation of treatment with Zytiga + prednisone . Is it possible that some specific sequence or combination of Zytiga, Enzalutamide, Provenge, and Chemotherapy might extend that median overall survival period? But Zytiga didn't meet OS. In other words, the FDA approved Zytiga solely on the basis of the effect on PFS. It is very important to understand that the all men in this trial were permitted to go on to other forms of treatment like Provenge, Chemo, Enzalutamide after they had progressive disease on either Zytiga + prednisone or Placebo + prednisone.
The FDA rejected the primary PFS endpoint request for Enzalutamide. Of course Medivation asks why Zytigapre-chemotherapy study with a primary PFS endpoint got an SPA but not pre-chemotherapy Enzalutamide study.
So I am not sure Medivation would want to unblind the Enzalutamide study without an SPA at interim without really strong OS data like J&J did.
The difference between the FDA’s decision for primary OS end point for Enzalutamide then Zytiga appears to have been driven by the result of the Provenge Phase III trial, which clearly demonstrated that PFS is not necessarily a surrogate for OS in chemotherapy-naive, metastatic prostate cancer. The decision about Zytiga trial was taken prior to availability of data from the Provenge Phase III trial. The decision about Enzalutamide was taken after those data were available.
Anyway I can't wait for Provenge+ Enzalutamide Trail start this year and result for Provenge+ Zytiga this year.
So in prostate cancer world it will be very important sequences and synergistics of treatments.

Post Edited (HOPENEVERDIE) : 2/10/2013 12:40:44 PM (GMT-7)

HopenEVERDIE

Take a look at the threads here on experiences with Xtandi. The side effects are pretty harsh

Bud

49packard,
Congrats all around. I hope you keep feeling as well as you have been. I got a 6 month shot of Lupron last month and it kicked me hard. Had a lot of hip and lower back pain, plus the fatigue that came with it. I am keeping my fingers crossed that Lupron does work for you and will continue to work for you.

Those of us who have had the Provenge treatment, first are depending on its success and second we need to continue to share our results with everyone so they can make their own informed choice if they want to proceed with the treatment. I made it 20 months post surgery with my PSA at <0.01 with the ultra sensitive test and then Santa Claus came and gave me some coal and took away the less than sign. So that triggered the Lupron and Cassodex journey that started in January.

I go in next week for my IMRT planning session and will start getting hit with radiation at the end of the month. I am getting cold feet about 12 weeks of IMRT and the possible SE after reading all of Purgatory's postings and other HW postings, but the statistics are quite compelling for starting radiation before the rise in PSA.

I hope it does not turn into the seven years you had with your trial studies or even like David's horrific experience, but since I am so high risk, I have to begin the next journey.

Best of wishes to you and your loved ones.

Dr. Cooperberg on Earlier Treatment With Sipuleucel-T
Matthew Cooperberg, MD, MPH
Published Online: Friday, February 15, 2013
Print
Email
Matthew Cooperberg, MD, MPH, Assistant Professor of Urology; Epidemiology & Biostatistics, University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, discusses the earlier administration of treatment with sipuleucel-T (Provenge) for men with prostate cancer.

Cooperberg believes that immunotherapies, such as sipuleucel-T, are best administered earlier in the treatment paradigm when the immune system is stronger and less cancer cells are present.

To examine this, a study conducted at the University of California, San Francisco looked at the neoadjuvant administration of sipuleucel-T. The primary endpoints for this study were immune parameters that related to immune activation by sipuleucel-T. Cooperberg believes that from a mechanistic standpoint, sipuleucel-T may be most effective when given as a neoadjuvant therapy in prostate cancer.

www.onclive.com/conference-coverage/gu-2013/Dr-Cooperberg-on-Earlier-Treatment-With-Sipuleucel-T

The Growing Understanding of the Potential Influence of Immunotherapy in Prostate Cancer
Ravi A. Madan, MD, and William L. Dahut, MD

"However, these studies also suggest that immune-based treatments may slow the tumor growth rate over time without leading to marked short-term tumor shrinkage (Figure), an effect that could lead to improved OS without improved time to progression (TTP, trajectory A in Figure). This is not the outcome generally seen with cytoreductive therapies, which have a transient effect on tumor growth rates (trajectory B in Figure). This mechanism of improved OS without improved short-term TTP suggests that the most prudent use of immunotherapies such as sipuleucel-T would be early in the disease process, which would allow sufficient time for any potential effect on tumor growth.

In an evolving clinical setting where multiple immunotherapeutic agents may be approved for the treatment of mCRPC, optimizing these therapies becomes a priority. Although combining therapies can have additive benefit, the immunologic effect of commonly used therapies in the management of prostate cancer has provided further impetus for the investigation of synergistic immune-based combination strategies. Even at sublethal doses, radiation has been shown to alter the phenotypic expression of malignant cells, up-regulating tumor antigens that can be targeted by immune cells previously activated by immunotherapy.

Androgen-deprivation therapy (ADT) can also enhance the immune response. Clinical data have demonstrated that ADT traffics T cells to the prostate and decreases immune tolerance to self-antigens overexpressed on prostate cancer cells. ADT also induces the thymus to produce naïve T cells that can be activated by immunotherapy.9 Given these effects, ADT combined with immunotherapy presents an attractive therapeutic opportunity. A recent study combining sipuleucel-T and ADT in patients with biochemical recurrence has completed accrual and results are pending (NCT01431391).

... In fact, an analysis of immune cells after 6 months of docetaxel-based therapy found no effect on immune-cell function. An ongoing trial investigating the sequential or concurrent use of abiraterone and prednisone with sipuleucel-T could provide clinical data that resolve these concerns (NCT01487863).

The ability to stimulate this type of precision immune response could have significant long-term clinical benefits for patients with early-stage disease, as well as for high-risk patients receiving radiation or for patients with biochemical recurrence receiving ADT. The ideal result would be slower disease growth in the years following initial treatment, perhaps limiting the need for more toxic therapies or substantially delaying clinically meaningful mCRPC.

As with any new therapy, demonstrating clinical effect is only the first step. The second, and perhaps most crucial, part of the process is determining how to optimize a new therapy in clinical practice. For immunotherapies, which may have continuous and evolving effects during a patient’s lifetime, the second step may pay significantly greater dividends than initial clinical trials have suggested."

gucasym.asco.org/growing-understanding-potential-influence-immunotherapy-prostate-cancer

Hi All: Just working around house ( chief house ***** ) and enjoying my Provenge. I just pasted my 8 th month of being on Provenge. My Lupron shot that I got Feb 1, 2013 has had its two weeks to kick in. A few more hot flashes plus sinus are draining.   I still feel GREAT. I checked into the immune system and what makes it works. Looks like I am eating most of what they suggest. I will be adding vitamin” C” 1000 mg to my pill list. 49 Packard

Glad you are feeling great ! Your name caught my attention, do you have a 49 Packard ? I have a 51 Packard that belonged to my father.

Nothing more awesome than a Packard. Always wanted one, its on my boy-toy wish list still.

david

 

Check my Packard out on my web site.

www.WfPCR.org

Mine is the black on on the top left side.

49Packard

In my last post about Richard Hamablet and his journey with Provenge reporter has mentioned Marie Huber (not by name) as a "scientist" that questions the efficacy of Provenge ( she worked for hedge fund, never was scientist, if she is a "scientist", then I think I will start calling myself a military pilot). I gave my opinion about it in another thread:

www.healingwell.com/community/default.aspx?f=35&m=2535800

and now more:

From the article " Building on Sipuleucel-T for Immunologic Treatment of Castration-Resistant Prostate Cancer ":
"Potential issues have been raised regarding the sipuleucel-T phase III trials. In particular, it was hypothesizedthat the observed difference in OS could have been due to a harmful effect of the control intervention in the ≥ 65-year-old control patients resulting from leukapheresis-induced immunodepletion. This
hypothesis has been refuted by experts in the field of cancer immunotherapy and the IMPACT authors...

The National Institutes of Health experience with serial leukapheresis procedures in more than 400 healthy subjects showed that the decreases in lymphocyte counts after 2 to 9 procedures were not clinically signifi cant, with no increased susceptibility to infectious diseases or cancer. Across the phase III trials, there was no evidence that leukapheresis led to immunodepletion. At 6, 14, and 26 weeks, median white blood cell, absolute neutrophil, lymphocyte, and monocyte counts remained within the normal range in each treatment
group. It is important to note that an increased rate of infections would be expected if patients in the placebo group had experienced clinically signifi cant immunosuppression. The incidence of infection-related
AEs was similar between the sipuleucel-T and control groups (27.5% vs 27.7%), and the majority (83.9%) of
those events were grade 1 to 2. Grade 3 to 5 infections were reported in 5.0% of patients who received
sipuleucel-T and in 3.3% of control patients."

www.healingwell.com/community/default.aspx?f=35&m=2629377

Meanwhile I recommend to read this article . It is very informative and interesting to read.

Recently, NCBI published Abstract "An Analysis of Leukapheresis and central venous catheter use in the randomized, placebo controlled, phase 3 IMPACT trial of Sipuleucel-T for metastatic castrate resistant prostate cancer.":
"Flanigan RC, Polcari AJ, Shore ND, Price TH, Sims RB, Maher JC, Whitmore JB, Corman JM.
Source
Loyola University Stritch School of Medicine, Maywood, Illinois, USA. [email protected]
Abstract

PURPOSE:
Sipuleucel-T is an autologous cellular immunotherapy. We review the safety of the leukapheresis procedure required for sipuleucel-T preparation and complications related to venous catheter use in the randomized, placebo controlled phase 3 IMPACT (IMmunotherapy for ProstAte Cancer Trial) study (NCT 00065442).
MATERIALS AND METHODS:
A total of 512 patients with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer were enrolled in the study. All patients were scheduled to undergo 3 standard 1.5 to 2.0 blood volume leukapheresis procedures at 2-week intervals. Leukapheresis related adverse events and those related to venous catheter use were reviewed. Immune cell counts were examined throughout the treatment course
RESULTS:
Of 512 enrolled patients 506 underwent 1 or more leukapheresis procedures and were included in this analysis. Adverse events were comparable between the sipuleucel-T and control arms. Leukapheresis related adverse events were primarily associated with transient hypocalcemia (39.3%). Most leukapheresis related adverse events (97%) were of mild/moderate intensity. Median white blood cell count and absolute monocyte and lymphocyte counts were stable and within normal ranges throughout the treatment course. Of all patients 23.3% had a central venous catheter placed primarily for leukapheresis. Patients with vs without a central venous catheter had a higher risk of infection potentially related to catheter use (11.9% vs 1.3%, p <0.0001) and a trend toward a higher incidence of venous vascular events potentially related to catheter use, excluding the central nervous system (5.9% vs 2.1%, p = 0.06).
CONCLUSIONS:
Adverse events related to leukapheresis are manageable and quickly reversible. The majority of patients can undergo leukapheresis without a central venous catheter. Central venous catheters are associated with an increased risk of infections and venous vascular events. Peripheral intravenous access should be used when feasible."

www.ncbi.nlm.nih.gov/pubmed/23253957

I would like to say about video of Richard Hamablet that when he went to MRI his cancer was gone and it was like miracle for him and he is hopeful it can help other men with cancer. His doctor said his prognoses is excellent and he would say that Richard will be around for years.

Post Edited (HOPENEVERDIE) : 3/3/2013 4:11:44 PM (GMT-7)