Second What-If Question: Role of Chemo

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Purgatory
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Date Joined Oct 2008
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   Posted 12/27/2010 9:54 PM (GMT -6)   

I didn’t want to blur the answers from my first “what if” question with this question.  I appreciate all the answers on the first part, which was about HT.  Now I have a question or two about chemo and PC.  I will say up front, while I understand the role of chemo and how effective it can be with breast cancer and some other cancers, I don’t understand its role or effectiveness in dealing with PC.

Kind of a two part question.

First, I assume that chemo is used with PC as a last resort, after a person normally has been through the HT route, and have become refractory to it.  I could even be wrong on this assumption, as I simply don’t know.  If this is the case, what is the real role of putting the patient at such a advanced stage through the rigors of chemo, if its not going to be effective at all.  I couldn’t imagine it doing much to extend lifetime at that point, and that the quality of life would have to be terrible, much worse than the side effects of HT or physical castration.  Am I missing something here?

Secondly, if my make believe patient bypassed HT altogether, after a failed primary and secondary treatment, leaving them incurable,  what would be the point of undergoing future chemo if the chemo itself would be of little effect?

Looking for any and all answers or opinions.

David in SC

 

Post Edited (Purgatory) : 12/27/2010 11:00:33 PM (GMT-7)


proscapt
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Date Joined Aug 2010
Total Posts : 644
   Posted 12/27/2010 11:46 PM (GMT -6)   
David -

There are a number of studies which use chemo adjuvant with HT and which show significantly extended survival times.

For example, look at this set of slide from Eisenberger at Hopkins (it is difficult to follow, since the speech is not there, but you can get a general idea.) www.urotoday.com/images/pdf_files/07.Eisenberger.ChemoRisk.pdf

Look at page 20-21 in particular. It describes a study of "high risk" patients where some were randomized to receiving adjuvant HT only, and some were randomized to adjuvant HT plus Mitoxantrone, a chemotherapy treatment.
Page 21 shows the results: media survival of 80 months for the ones who got chemo vs. 36 months for the other group. At 8 years it looks like 40% of the ones receiving chemo were alive vs. 15% of the other group.

Other studies show similar gains with chemo used in conjuction with HT, as best I can decipher the PPT.

Here's another article you might want to look at:

Early Chemotherapy in Prostate Cancer: Adjuvant Chemotherapy After Surgery or Radiotherapy
Nat Clin Pract Urol. 2008;5(9):486-493. © 2008 Nature Publishing Group
David Mazhar, Addenbrooke’s Hospital, Cambridge, England
Jonathan Waxman, Hammersmith Hospital, London, England

(I realize you're past the adjuvant stage, but still the fact that it's helpful there is encouraging)

Summary
A considerable proportion of men with clinically localized prostate cancer are not cured by surgery or radiotherapy, and hormone therapy for advanced disease is also not curative. Given the demonstrable efficacy of chemotherapy in hormone-refractory disease, there is an interest in examining the curative potential of chemotherapy when administered early in the natural history of prostate cancer. It is hoped that chemotherapy could be used with hormone therapy and in the adjuvant setting, as is the case in many other solid tumors, in patients with 'high-risk' prostate cancer who are undergoing primary radical prostatectomy or radiotherapy. Early phase clinical trials have shown that using docetaxel as neoadjuvant or adjuvant therapy is safe and feasible. In the neoadjuvant setting, tumor shrinkage, serological response, there is some evidence of pathological downstaging. Several randomized trials are ongoing, and it is anticipated that the results of these studies will help to identify whether the early use of chemotherapy in early prostate cancer is beneficial.


In particular, note this section:

Chemotherapy in Hormone-refractory Prostate Cancer

Studies in the past few years have highlighted the value of chemotherapy in progressive prostate cancer. In the 1990s, Tannock et al. conducted a study in which patients with hormone-refractory prostate cancer were randomly assigned to receive either mitoxantrone and prednisone or prednisone alone. This study showed improvement in patients' quality of life after combination therapy with mitoxantrone and prednisone, although this treatment regimen did not prolong survival -- the median survival of patients in both treatment groups was 10 months.

The treatment options for patients with prostate cancer have changed recently. In October 2004, two publications in the New England Journal of Medicine indicated that the survival of patients with progressive prostate cancer could be improved with docetaxel chemotherapy given in combination with either steroids or with additional cytotoxic therapeutic drugs.[2,3] In these two large studies, patients who received docetaxel chemotherapy had a median survival of 18.9 months from initiation of treatment compared with 16.5 months in patients who received mitoxantrone chemotherapy. This difference represents a significant extension of life. Many authors have compared the survival data from these patients treated with docetaxel with results obtained in Tannock and colleagues' 1996 mitoxantrone study, and have suggested that the advantage of docetaxel in the more recent studies might be understated. Others have commented that the survival time of 16.5 months in patients who received mitoxantrone, as compared with 10 months in the original mitoxantrone study, is an indication of better palliative care. Regardless of this comment, the use of docetaxel chemotherapy certainly represents a substantial advance in the treatment options for patients with prostate cancer, and has become the standard of care for patients with hormone-refractory disease.

Clinicians are now becoming interested in moving docetaxel treatment into earlier stages of prostate cancer. Randomized phase III trials are underway examining the role of docetaxel in patients with locally advanced or metastatic disease who are starting or who have just recently started hormone therapy. Patients are usually better candidates for cytotoxic therapy at this stage of cancer than when their disease becomes hormone refractory. Patients with localized disease and high-risk features in neoadjuvant and adjuvant settings also present opportunities for study. There are currently models of an integrated approach to management for several other malignancies, such as breast and colon; can this combination method also be applied to prostate cancer?


My interpretation of all this is that using chemo after failure of HT seems to only provide a few more months of life, but using chemo in conjunction with HT an early stage could provide a much bigger benefit, including a greatly increased chance of additional years of life. That said, I have not made a detailed study of this, and there could be many considerations in addition to the ones I have found.

Geebra
Regular Member


Date Joined May 2009
Total Posts : 476
   Posted 12/28/2010 3:06 AM (GMT -6)   
David,

I am not sure how to answer this. On one hand, I saw my mother in law go through chemo at a late atage uteran cancer only to make her last weeks more miserable.

On the other hand, I participated in a clinical trial for neoadjuvant chemo. My tumor was reduced by more than half, while I tolerated the treatment well and had relatively minor side effects.

So I guess I agree with proscapt - chemo make sense in an earlier setting.

Greg.
Father died from poorly differentiated PCa @ 78 - normal PSA and DRE
5 biopsies over 4 years negative while PSA going from 3.8 to 28
Dx Nov 2007, age 46, PSA 29, Gleason 4+4=8
Decided to participate in clinical trial at Duke - 6 rounds of chemo (Taxotere + Avastin)
PSA prior to treatment 1/8/2008 is 33.90, bounced on 1/31/2008 to 38.20, and down at the end of the treatment (4/24/2008) to 20.60
RRP at Duke (Dr. Moul) on 6/16/2008, Gleason downgraded 4+3=7, T3a N0MX, focal extraprostatic extension, two small positive margins
PSA undetectable for 8 months, then 2/6/2009 0.10, 4/26/2009 0.17, 5/22/2009 0.20, 6/11/2009 0.27
ADT (ongoing, duration TBD): Lupron started 6/22/2009
Salvage IMRT to prostate bed and pelvis - 72gy over 40 treatments finished 10/21/2009
PSA 6/25/2009 0.1, T=516, 7/23/2009 <0.05, T<10, 10/21/2009 <0.05, T<10

zufus
Veteran Member


Date Joined Dec 2008
Total Posts : 3149
   Posted 12/28/2010 7:55 AM (GMT -6)   
It varies alot like in any PCa scenario as to at what stage and possible results using chemo's.
It is not always used as last resort useage, but is more commonly seen used as such. It can drag down your immune system and can be a big trade off as to quality of life and return on investment (amount of time you may have bought). There are all kinds of chemo's now, with combos used within them and now Cabitzitaxel and such. They can render different results, to some degree....so hopefully your doc is well schooled in the nuainces of variations for your sake. Some docs are staided in what the use or do, maybe not intentional agenda but almost as ridiculous. Like some only use Lupron and never look elsewhere or consider anything else as useful, or course they are blinded perhaps by the $$$$. Plenty to made off chemo therapies, which for PCa in general are not all that great and not found curative to my knowledge...EVER!

In the very end even though known to be palliative in useage, some people wish to try and live longer and even if it is a few months. Maybe there is a wedding or event they do not wish to miss, let alone day to day living. Choices exist and all the docs are not equal in knowledge, wisdom and experiences. Like Dr. Strum mentioned 10-15% maybe experts, 70% are average and 10-20% are dangerous (aka-Losers). I believe he knows the score. You can believe whatever you wish, just question everything and all the time and you will see that is worthy of your time. The average cancer patient in the USA (generality) is worth something like $300-400,000 dollars in billing. They love us to the max.
Dx-2002 total urinary blockage, bPsa 46.6 12/12 biopsies all loaded 75-95% vol.; Gleasons scores 7,8,9's (2-sets), gland size 35, ct and bone scans look clear- ADT3 5 months prior to radiations neutron/photon 2-machines, cont'd. ADT3, quit after 2 yrs. switched to DES 1-mg, off 1+ yr., controlled well, resumed, used intermittently, resumed useage

tarhoosier
Regular Member


Date Joined Mar 2010
Total Posts : 481
   Posted 12/28/2010 9:46 AM (GMT -6)   
The response rate to Taxotere is just like any other treatment for this or any other disease; variable. What is interesting about the 2003 TAX 327 study was that FOR THOSE WHO RESPONDED TO THE DRUG (>50% psa response) the median survival was >30 months. This group was 50-60% of the whole trial. The trial had to include all patients, with those who withdrew, could not resolve side effects, died of all causes, had little to no response, all added in to the total.
Now we know that there are other options. Charles Myers states, in a personal communication, that he has taken Tax resistant patients and has a 40 month median survival with no deaths for those beyond 40 months. This is with estrogen compounds, leukine (sagromostim) and ketoconazole combined as his therapies. He also says that within the first few treatments of Tax that the response can be identified and with no response he shifts patients to another chemo until a response is reached. This was not done for those on the TAX 327 trial.
It is true that for those not healthy enough to deal with the rigor of such a chemo regime the choices today are investigational drugs: Orteronel (TAK-700), MDV-3100, Abiraterone, XL-184, ARN 509, Alpharadin, TOK-001, et cetera.

Purgatory
Elite Member


Date Joined Oct 2008
Total Posts : 25364
   Posted 12/28/2010 12:48 PM (GMT -6)   
pro - you got a lot of good numbers for me to digest there on the subject, will have to ponder that a while.

greg - that's good, you show 2 different appliations and 2 different resuts

zufus - wouldnt it be nice, if a single element of PC could be the same and consistent each time. The money part is hard to deny, I am loved by my doctors, but no fool, I realize they love the insurance I have had all along. My PC journey, in round list prices ,including all surgeries and radiation is above $530K, and thats not counting any test, anethesia, bloodwork, meds, follow up visits, etc. Its nuts.

tar - from what i have read of tax, pretty potent stuff with a lot of side effects, most of them well known. the newer generation drugs you mention - isnt the jury out on most of them?

________________________

so, without putting words in anyone's mouth, are we saying that chemo alone for PC, not in combination with other drugs or HT, is pretty well a dead end street buying the most minimal time in life extension with the most detriment to QOL issues? Or am I reading too much into it?
Age: 58, 56 dx, PSA: 7/07 5.8, 10/08 16.3
3rd Biopsy: 9/08 7 of 7 Positive, 40-90%, Gleason 4+3
open RP: 11/08, on catheters for 101 days
Path Rpt: Gleason 3+4, pT2c, 42g, 20% cancer, 1 pos marg
Incont & ED: None
Post Surgery PSA: 2/09 .05,5/09 .1, 6/09 .11. 8/09 .16
Post SRT PSA: 1/10 .12, 4/8 .04, 8/6 .06 11/10 Not taking it
Latest: 6 Corr Surgeries to Bladder Neck, SP Catheter since 10/1/9, SRT 39 Sess/72 gy ended 11/09, 21 Catheters, Ileal Conduit Surgery 9/23/10

tarhoosier
Regular Member


Date Joined Mar 2010
Total Posts : 481
   Posted 12/28/2010 2:11 PM (GMT -6)   
Investigational drugs, are just that: under investigation in trials. The ones I mentioned are some of the most promising, in my amateur opinion. For those unable or unwilling to go the Tax route, a chemo naive trial patient may have fewer trial options. It is possible that some patients who refuse chemo or are unfit may be considered as post chemo for trial status in a few cases.

zufus
Veteran Member


Date Joined Dec 2008
Total Posts : 3149
   Posted 12/28/2010 3:58 PM (GMT -6)   
tar- good general info you had, good mention from Dr. Meyers and his experiences which some should note when considering using such

purg- you are the 1/2 million dollar man....I doubt you can run faster like on the old t.v. show.

pro- always worth looking at web references as you showed some

Purgatory
Elite Member


Date Joined Oct 2008
Total Posts : 25364
   Posted 12/28/2010 5:23 PM (GMT -6)   
sorry zufus, can't run worth a crap. barely can walk these days without my trusty cane to keep me from falling over.
my previous 3x with cancer would easily add another 400k or more to the tab. i know i am not worth this kind of money
Age: 58, 56 dx, PSA: 7/07 5.8, 10/08 16.3
3rd Biopsy: 9/08 7 of 7 Positive, 40-90%, Gleason 4+3
open RP: 11/08, on catheters for 101 days
Path Rpt: Gleason 3+4, pT2c, 42g, 20% cancer, 1 pos marg
Incont & ED: None
Post Surgery PSA: 2/09 .05,5/09 .1, 6/09 .11. 8/09 .16
Post SRT PSA: 1/10 .12, 4/8 .04, 8/6 .06 11/10 Not taking it
Latest: 6 Corr Surgeries to Bladder Neck, SP Catheter since 10/1/9, SRT 39 Sess/72 gy ended 11/09, 21 Catheters, Ileal Conduit Surgery 9/23/10

proscapt
Veteran Member


Date Joined Aug 2010
Total Posts : 644
   Posted 12/28/2010 8:09 PM (GMT -6)   
Purg -

Tar's point about difference in medians is worth thinking about more carefully. When news media report only the median survival between the treatment and control group it can conceal some important information -- particularly in cases when only a small percentage are responsive, but those who are responsive are VERY responsive.

Hypothetical example:

A group of 200 people, half get the drug and half don't.
In the Control group: 100 people, no treatment, their median survival is 12 months.
In the treatment group:
25 of them respond, and each of them lives 3 years.
75 of them don't respond, and each of them lives 12 months.

The median lifetime in the treatment group as a whole is still 12 months!!!!! A very misleading number!

So let's say the drug has nasty side effects which go away when you stop taking the drug.

The smart thing to do is you start the drug and monitor closely to see if it is working. ; if it doesn't do anything in a month or two you quit and the side effects go away. If it does work, it buys you three years, and you may decide it's worth the side effects for three years of life.

Lies, darn lies, and statistics, as they say. In my opinion you gotta look at the curves of survival over time.

Purgatory
Elite Member


Date Joined Oct 2008
Total Posts : 25364
   Posted 12/28/2010 8:26 PM (GMT -6)   
pro - thats a pretty good analysist, still thinking about what you posted
Age: 58, 56 dx, PSA: 7/07 5.8, 10/08 16.3
3rd Biopsy: 9/08 7 of 7 Positive, 40-90%, Gleason 4+3
open RP: 11/08, on catheters for 101 days
Path Rpt: Gleason 3+4, pT2c, 42g, 20% cancer, 1 pos marg
Incont & ED: None
Post Surgery PSA: 2/09 .05,5/09 .1, 6/09 .11. 8/09 .16
Post SRT PSA: 1/10 .12, 4/8 .04, 8/6 .06 11/10 Not taking it
Latest: 6 Corr Surgeries to Bladder Neck, SP Catheter since 10/1/9, SRT 39 Sess/72 gy ended 11/09, 21 Catheters, Ileal Conduit Surgery 9/23/10

Jerry L.
Veteran Member


Date Joined Feb 2010
Total Posts : 3049
   Posted 12/28/2010 8:32 PM (GMT -6)   
Proscapt,

Interesting info.

It will also be interesting to see if the early use of drugs like Abiraterone (and perhaps as adj. HT) will show increased survival rates as well.
Nov. 2009 Dx at Age 44
Dec. 2009 DaVinci Robotic Surgery
Jan. 2010 T3b, Gleason 9
Feb. 2010 Adjuvant Radiation

PSA History:
-----------------
Nov. 2009 4.30
Feb. 2010 <.05
May 2010 <.05
Aug. 2010 <.05
Nov. 2010 <.05

proscapt
Veteran Member


Date Joined Aug 2010
Total Posts : 644
   Posted 12/28/2010 9:30 PM (GMT -6)   
Good recap of current innovative chemo agents and combinations now under test: Update on options for treatment of metastatic castration-resistant prostate cancer full text available free at www.ncbi.nlm.nih.gov/pmc/articles/PMC2895780/?tool=pubmed


Jerry - here's latest encouraging data on Abiraterone:

Phase III data for abiraterone in an evolving landscape for castration-resistant prostate cancer.
2010 Nov 18.


Pal SK, Sartor O. -- Division of Genitourinary Malignancies, Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Los Angeles, CA, United States.

At the 2010 meeting of the European Society for Medical Oncology (ESMO), a landmark development in prostate cancer therapy was unveiled. In a phase III study, the CYP17 inhibitor abiraterone yielded a survival advantage over placebo in patients with metastatic castration-resistant prostate cancer (mCRPC) who had progressed despite prior docetaxel therapy. The data for abiraterone follow the publication of successful phase III studies earlier this year supporting two mechanistically distinct agents-namely, the novel taxane cabazitaxel and the autologous dendritic cell vaccine sipuleucel-T. A challenge that lies ahead for the scientific community is to discern the appropriate positioning of abiraterone in an increasingly crowded therapeutic landscape. Several ongoing trials are examining the agent in earlier settings (i.e., a phase III in mCRPC pre-docetaxel, and smaller studies in combination with radiation therapy or as neoadjuvant pre-surgery for localized disease). Herein, several potential strategies for abiraterone are presented to clarify the clinical utilization of this agent in the future.


I like the idea of "increasingly crowded therapeutic landscape." :-) Lots to choose from. The scientist's challenge is our blessing.

Post Edited (proscapt) : 12/28/2010 8:40:43 PM (GMT-7)


gibson00
Regular Member


Date Joined Nov 2009
Total Posts : 212
   Posted 12/29/2010 2:42 PM (GMT -6)   
Just to add...
My father's treatment as part of a study was Lupron, and Radiation along with once per week Taxotere. Not sure what the Taxotere dose was, but they said it was low.
He was stage 3 w/Gleason 9&10......now they can't detect any cancer, PSA almost undetectable (<.003). They considered it a, and I quote, 'small miracle'. Knock on wood.......
He does have sore feet/toes neuropathy, which may have been caused by the taxotere.
I don't think the study is complete, so no official numbers..
Father 65 y/o at diagnosis November 2009
Gleason 9 & 10, stage 3 - seminal vesicle involvement
Two TURPs mid Nov. 2009
Foley Catheter
Casodex for last two weeks of November '09, then Lupron.
Suprapubic Catheter March 18th, but blocked right away, back to Foley...
Started IMRT March 25th, Chemo on hold due to catheter bleeding issues, etc.
Ended IMRT and Chemo (Taxotere) late May
Mid-July - pain finally better controlled with Fentanyl patch
Late July - Superpubic Cath. removed, peeing normal again
July 21 - PSA .21

Post Edited (gibson00) : 12/29/2010 1:49:37 PM (GMT-7)


Purgatory
Elite Member


Date Joined Oct 2008
Total Posts : 25364
   Posted 12/29/2010 3:26 PM (GMT -6)   
that's really good news to hear about your father, gibson.
Age: 58, 56 dx, PSA: 7/07 5.8, 10/08 16.3
3rd Biopsy: 9/08 7 of 7 Positive, 40-90%, Gleason 4+3
open RP: 11/08, on catheters for 101 days
Path Rpt: Gleason 3+4, pT2c, 42g, 20% cancer, 1 pos marg
Incont & ED: None
Post Surgery PSA: 2/09 .05,5/09 .1, 6/09 .11. 8/09 .16
Post SRT PSA: 1/10 .12, 4/8 .04, 8/6 .06 11/10 Not taking it
Latest: 6 Corr Surgeries to Bladder Neck, SP Catheter since 10/1/9, SRT 39 Sess/72 gy ended 11/09, 21 Catheters, Ileal Conduit Surgery 9/23/10
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