RE: [SPAM] Re: Re: Universal Medicaid and Medicare Coverage for Provenge - We Need Your Help

[Guest guest]

The URL I posted led to the following paper back in February, and granted, in the report was the evidence that one man experienced at least a four year survival.š Let’s not down-play the importance that one man experienced.š Likely that will not be the case for all men, but it will likely be the case for more than that one man.š Sipuleucel-T (APC8015)In the late 1990s, researchers began to investigate the concept of tumor-specific immunity, whereby an immune response is stimulated in order to target tumor cells for destruction.[1] This idea was applied to the development of sipuleucel-T (Provenge). In the course of treatment with Provenge, the patient’s antigen-presenting cells (APCs, specifically dendritic cells) are collected via leukapheresis and then loaded ex-vivo with a fusion protein consisting of prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GM-CSF). After culturing this fusion protein with the dendritic cells, the product is then re-infused into the patient, activating T-cells via class I and class II HLA molecules and resulting in a beneficial immune response against PAP.In a phase I-II trial, 31 patients were treated with sipuleucel-T.[2] The phase I portion examined patient response to dose escalation in three tiers of patients with metastatic CRPC, all of whom had undergone androgen deprivation with androgen blockade and subsequent antiandrogen withdrawal. The most common adverse reactions were fever, myalgia, and mild urinary complaints. Only three patients were noted to have had a prostate-specific antigen (PSA) decline of ™ 50% from baseline, despite all patients exhibiting a measurable immune response to the fusion protein and 38% developing an immune response specific to PAP. While some patients demonstrated a clear clinical response in the form of a significant drop in PSA, the authors noted that PSA may not be a valid indicator of meaningful anticancer activity for immune-based therapies as future trials would eventually demonstrate.A second phase II trial of sipuleucel-T in 21 patients with metastatic CRPC was conducted and resulted in a similar overall lack of effect on PSA levels. However, one patient exhibited a potent, durable biochemical response, with PSA falling from 221 ng/mL to undetectable and sustaining these levels for more than four years.[3] To address the potential inadequacy of PSA as a measure of meaningful clinical activity, investigators altered the definition of “progression” from a biochemical change (in PSA level), to objective enlargement of soft tissue disease or the appearance of two or more new lesions on radionuclide bone scan. Using this new definition, median time to progression was 118 days.A phase III trial enrolled 127 asymptomatic men with metastatic CRPC randomized in a 2:1 ratio to receive either sipuleucel-T or placebo. The trial was designed to measure a primary outcome of time to progression (defined as pathologic fracture, spinal cord compression, new-onset pain associated with metastasis, two or more lesions on bone scan, or > 50% increase in measurable cancer burden).[4] Overall, there was no significant difference in time to progression between the two treatment arms, but there was a 4.5 month improvement (P = .01) in overall survival in the sipuleucel-T arm. However, because this study was not originally designed to detect an increase in overall survival, more evidence was requested to support its use in men with CRPC when initially evaluated by the FDA for approval in 2007.To bolster proof of clinical efficacy, investigators proceeded with a second phase III, double-blind, placebo-controlled, multicenter trial of sipuleucel-T that was designed to measure its effect on overall survival, and the results were published in July 2010.[5] In this trial, 512 patients were randomized in a 2:1 ratio to receive either sipuleucel-T or placebo. The study detected a 4.1-month improvement in overall survival over placebo, despite allowing 109 of 171 patients in the placebo group to cross over and receive salvage sipuleucel-T (prepared and cryopreserved at the time of placebo preparation). Adverse events in the treated group were primarily limited to fever, chills, and headache at or near the time of the infusion. Similar to previous studies, there were no differences in the time to disease progression (measured radiographically at 6, 14, 26, 34 weeks and every 12 weeks thereafter) between the two groups.Investigators attributed the discordance between the observed survival benefit and the lack of effect on disease progression to a possible class effect, as a similar phenomenon has been reported in a study on poxviral-based PSA-targeted immunotherapy (PROSTVAC-VF).[6] Similarly, other studies of metastatic CRPC have shown a lack of correlation between disease progression and overall survival.[4,7] Sipuleucel-T was approved by the FDA in April of 2010 for the treatment of metastatic CRPC which is asymptomatic or minimally symptomatic.Chuck Always as close as the other end of your computer to help address any prostate cancer concerns. " What you leave behind is not what is engraved in stone monuments, but what is woven into the lives of others. " (Chuck) Maack/Prostate Cancer Advocate/Mentor Wichita, Kansas Chapter, Us TOOBiography: http://www.ustoowichita.org/leaders.cfm?content=bio & id=1 Email: maack1@... Chapter Website " Observations " : http://www.ustoowichita.org/observations.cfm From: ProstateCancerSupport [mailto:ProstateCancerSupport ] On Behalf Of CochraneSent: Sunday, April 24, 2011 7:10 PMTo: ProstateCancerSupport Subject: [sPAM] Re: Re: Universal Medicaid and Medicare Coverage for Provenge - We Need Your Help I now realize that Chuck meant to report that " one man " and not " Some men " can have extended survival Information in the following indicates that some men can have their lives extended by as many as 4 years following administration of sipuleucel-T/Provenge, so the “4 months” of survival should not be the argument against its availability. http://www.cancernetwork.com/prostate-cancer/content/article/10165/1771420 It is much easier for those not in the circumstances of requiring Provenge to argue against its availability because of cost. Take the time to add up the cost of the medications involved in chemotherapy to prolong the lives of those with hormone/castration-resistant prostate cancer (HRPC/CRPC) – should we just take away chemotherapy to prolong lives as well? The same argument of cost would still apply. No, we certainly should not. I have been blessed with a prolonged life of over 18 years of prostate cancer and over 14 years of androgen deprivation to provide me that extended life. Add up the cost of medications over those years, and they, too, will reach unbelievable numbers. But I still live and still must look forward to other medications to prolong my life when my cancer becomes HRPC/CRPC. And I thank The Good Lord for my insurance covering these expenses. Talk about an economic disaster – my family would most certainly have faced such a disaster without insurance. And I pray daily for those who have been diagnosed with prostate cancer and have no insurance. Back in February I forwarded the below to this forum that leads to a very reasonable discussion regarding Provenge, its cost, how economics are playing a role in its availability, and how patients/families have clung to the hope of prolonging life. As I noted, a reasonable discussion, but somewhat saddening as well when we recognize the impact it can have on families and THEIR economics when health insurance fails to cover the medication. From: pcan-bounces@... On Behalf Of Kathy MeadeSent: Monday, February 07, 2011 10:05 AMTo: VPCCLegislativeAdvocacy; VPCC_BOARD ; VAPCACOALITION ; NASPCC ; Pcan; Patient Advocates in Research; 'Prostate Cancer Action'; 'PCa Roundtable'Subject: [PCAN] February 4, 2011 ~ Medical Cost-Benefit Ethics | Religion & Ethics NewsWeekly Provenge http://www.pbs.org/wnet/religionandethics/episodes/february-4-2011/medical-cost-benefit-ethics/8092/ or if that won't open because of length, try http://tinyurl.com/477buzr Video about medical ethics with Provenge as an example. Kathy For those of us who are not in the shoes of those whose cancer has moved them to the “hope” of Provenge to give them either a month or years of continued life, we have no reason to make comment one way or the other over its expense. Chuck Always as close as the other end of your computer to help address any prostate cancer concerns. " What you leave behind is not what is engraved in stone monuments, but what is woven into the lives of others. " (Chuck) Maack/Prostate Cancer Advocate/Mentor Wichita, Kansas Chapter, Us TOOBiography: http://www.ustoowichita.org/leaders.cfm?content=bio & id=1Email: maack1@...Chapter Website " Observations " : http://www.ustoowichita.org/observations.cfm From: ProstateCancerSupport [mailto:ProstateCancerSupport ] On Behalf Of Sent: Sunday, April 24, 2011 4:05 PMTo: ProstateCancerSupport Subject: Re: Universal Medicaid and Medicare Coverage for Provenge - We Need Your Help :Several weeks ago I started a thread titled " Spend $93,000 to extend life by 4 months? " on this forum as well as the PCa newsgroup. Of those that noted an opinion 100% said that $93,000 was unreasonable and if it were their own money they wouldn't do it.The medical industry can invent treatments much, much faster than we as a society can pay for them. We have to put our foot down and say no to expensive, limited effect treatments.Sure we can quibble about means versus medians and whether the study focussed on almost terminal patients. The bottom line was very little improvement in lifespan (versus a placebo) for a lot of money.I would welcome a well designed study that is based on HT resistant patients but who have limited metastisis so we can see if there is any significant improvement in lifespan for those with years to live. But until then, no..

[Guest guest]

Chuck Maack wrote:

> The URL I posted led to the following paper back in February,

> and granted, in the report was the evidence that one man

> experienced at least a four year survival. Let’s not down-play

> the importance that one man experienced. ...

We have seen how the response to specific treatments varies

tremendously from one cancer patient to another.

I think what we really need now is for someone to study that man

and figure out what is different about him that produced the four

year survival, and also to study the men who got little benefit

and find out what they had in common.

This is one of the frontiers in current cancer research. Some

day doctors will be able to analyze a patient's DNA and the

molecular biology of his specific tumor cells and will be able to

tell exactly what treatments the patient will and won't respond

to. When we reach that day, costs will go down because we won't

apply expensive treatments to patients who can't benefit from

them. Side effects will go down because we won't apply toxic

treatments to patients who can't benefit from them. Survival

will go up because the patients who can benefit from a treatment

will get that treatment and get it earlier than would be the case

today.

It will take time, hard work, insight, expertise, a lot of

experience with each treatment, and a little luck.

I don't know if four months of median life extension is worth

$93,000 or not, but I do wish to continue with the development,

the study, and the application of Provenge in hopes that, over

time, we'll be able to get longer and longer responses from it.

Alan