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At what point should chemo be used to treat PC? Did things change in 2015?

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Posted 9/18/2015 12:20 AM (GMT 0)
Given the recent studies on the use of chemo with prostate cancer, I thought it might be good to document what the current data shows as of September, 2015. I also thought it might be a good discussion topic. Let's start the discussion with these 2 questions? Please include any studies and thoughts about chemo and PC:

1. Is chemo effective at the time of primary treatment? Meaning, should it be combined with surgery or radiation?

2. Is there any advantage to add chemo at the start of hormone therapy?

Thanks,
Jerry
Posted 9/18/2015 1:36 AM (GMT 0)
The CHARTED study last year on early Taxator chemo for high risk patients was so successful it was stopped early.
There is a presentation be Nick Vogelzang on the Prostate Advocates Forum on the study.
Posted 9/18/2015 2:20 AM (GMT 0)
Thanks John.

The CHAARTED trial showed that those men with high volume disease had a huge benefit. Low volume disease is tbd.

It seems to me that we used to think that chemo wasn't very beneficial for prostate cancer because prostate cancer is generally slow growing and chemo seemed to be for more aggressive cancers. Is this no longer the case?
Posted 9/18/2015 4:19 AM (GMT 0)
Jerry
Good idea to gather this info on one thread.
Although I don't have any data to back up the following conversation, I think it's worth sharing. My doctor at Mayo told me right away (before I started chemo and about 15 months before the published CHAARTED study) that he and other docs used to treat guys with aggressive disease with chemo. Then, he said that the medical community didn't like that he was over treating PCa guys and he seemed to back off of the approach. But, when we were discussing the option to try chemo after 6 months of Casodex and Firmagon, he noted that many of the guys that had aggressive disease and had gone through chemotherapy years earlier were still around. This was appealing for obvious reasons especially when we were hearing from other docs that 2-3 years would be a good run with my diagnosis. I did 3 rounds of Taxotere and 4 rounds of Cisplatin/Etoposide in 2013. This was followed up by 2 surgeries in Early 2014 (RP & Thymectomy) as well as 36 treatments IMRT. I am now 4 months shy of 3 years and my disease is as under "control" as it has been since my diagnosis. I'm still on Casodex and Lupron but hoping for a vacation if all stays good through August of 2016.
Posted 9/18/2015 4:35 PM (GMT 0)
Jerry.
It makes perfect sense to start early as there is no type of cancer in which late intervention with chemo drugs is more effective than early intervention.
The issue remains that of over treatment, but with high risk PC, the risk of death more than offsets the risk of early treatment side effects. You wouldn't use chemo on low or intermediate risk where the risk of death is low.
Posted 9/18/2015 4:49 PM (GMT 0)
All I can add, from the PCRI conference last weekend, was the recognition that chemo is delayed sometimes because of the stigma, and it should not be. Sooner the better in some patients, darn the stigma.

====================================================

Age 64 in 2015
12/02 PSA 2.9 age 51
9/03 BX/DX, Gleason 6, 4 of 12 cores
9/03 Low dose brachytherapy
5/08 PSA nadir 1.1
12/08 PSA 1.8
2/09 BX/DX, Gleason 8, 1 of 12 cores
6/09 Hyperthermic Radiation, Hormone (short term), IMRT (10 fractions) spring 2009
10/09 PSA nadir < 0.1 10/09 through 01/12
4/12 PSA 0.2
3/14 PSA 2.9
5/14 C11 Acetate PT/CT, found 2.0 cm lymph node
5/14 Lupron/Casodex (9 months)
8/14 nadir <0.01
2/15 SBRT to node, at UCSD
3/15 PSA 0.02,T=0
6/15 PSA<0.015,T=105 (yippee!)
Posted 9/18/2015 10:15 PM (GMT 0)
Hello Friends,

I was in the very FIRST wave of patients treated with Taxotere in the summer of 2014, immediately following the release of the CHAARTED study which showed survival benefit for chemo treatments in addition to hormone shots for advanced prostate cancer.

This "new plan" for chemo treatments got approved and I immediately started the treatments following the release of the CHAARTED study.

I went to work every single day during chemo treatments, without fail, for which I was thankful.

The Taxotere chemo treatments added to the hormone shots brought my PSA down below 0.10, the lowest level I had experienced.

Because I had just started hormone shots a few months earlier after being diagnosed, I am one of those patients that got the chance to actually SEE that adding the Taxotere chemotherapy infusions onto the hormone shots brought my PSA even lower than the shots alone could.

Some of my friends diagnosed AFTER me were started immediately on both hormone shots and chemotherapy, so they will never fully know which treatment did them the most good, other than they are benefiting immediately from two simultaneous treatments.

Since then, other friends of mine have pursued the Taxotere treatments and experienced some similar successes. I hope every day that others will be helped by pursuing these early chemo treatments, when it fits that patient's situation.

I realize each case is different, but I think my experience in seeing the effect of the Taxotere chemotherapy added onto the hormone shots is important for me to share with others, because I watched the PSA drop even lower AFTER we added the chemo treatments. Even though chemo treatments can be a rough road, I have to consider myself an advocate for chemo treatments. I am living proof that they can be helpful in the right situation.

The science is continually evolving and we have ALL played a part in that as our treatments continue ! Even our doctors are learning from each one of us, and helps lead them on to help future patients --- I think that's an important sentiment to remember. We have to do what we can now, as others did before us, to help others in the future.

Thanks for starting this thread,
Cyclone

Post Edited (ISU-CycloneFan) : 9/22/2015 10:18:50 AM (GMT-6)

Posted 9/19/2015 7:36 AM (GMT 0)
Jerry,
That is the route MrWW took. Early Taxotere/Carboplatin in January 2012. He was scheduled to begin in September 2011 as immediate 1st treatment with Lupron and Casodex but his oncologist said the data was just not their to support it (meaning it was out of protocol).

He had 3 rounds of Taxotere/Carboplatin along with Lupron and Casodex and as soon as his blood count was semi improved, he went through IMRT as his choice of consolidation. Surgery would have removed his bladder too.

His oncologist pushed hard for the early use of chemo due to visceral mets, positive seminal vesicles, and positive lymph nodes. The oncologist was hoping to catch anything that was floating around via his blood.

With the exception of immediate Lupron and Casodex.... pretty much all of his treatment was outside of normal protocol. He was more than willing to try things early, as the 3-5 years they gave him initially were totally unacceptable to us.

When on chemo, we would drive to MD Anderson on Thursday, chemo was administered on Friday and since he was pumped up from the dexamethasone we would drive home on Saturday and on Sunday he would crash. He would be back to work on Monday.

No regrets in treatment choices.
Posted 9/21/2015 11:26 PM (GMT 0)
The E3805 (CHAARTED) trial is as Jerry says.

YES:
4 identified bone lesions or visceral disease (spread to organs distant to the point of origin.)

NO:
anything less

The choice to do a harsh chemo regimen is a very tough call for men that had positive nodes but not meeting the E3805 criteria where success was seen. A docetaxel regimen can be more harmful than the disease when such treatment is not absolutely necessary.

That stated, we are still getting data at SWOG on E3805 and time may in fact change the approach. But for now ~ nothing has changed.
Posted 9/22/2015 1:22 AM (GMT 0)
There was a new study this year - the early results of the STAMPEDE trial. It showed a survival benefit vs ADT of 21 months for early use if there were metastases (M1 - not only N1). However, there was no survival benefit if there were no metastases. We haven't yet seen the breakdown for few vs multiple mets, and as I said, these are very early results. There was another randomized clinical trial in 2013, GETUG-AFU15, that comes to contradictory conclusions, possibly because it didn't include as many patients as CHAARTED that had high volume of mets. It did, however, show a benefit in progression-free survival, but not in overall survival.

Another interesting use of chemo is in adjuvant treatment to radiation and ADT for high-risk (non-metastatic) PC. So far, the benefits have not been meaningful enough to justify such use.

Another potential benefit seen in a recent study is that it may, in some cases, restore sensitivity to Xtandi and/or Zytiga after the cancer has become resistant to those.

There have also been some encouraging findings about earlier use of Jevtana (before Taxotere resistance sets in.)

My guess, and it's only a guess, is that at some point in its natural history after metastases have multiplied, some of the cancer evolves to a stage that is particularly sensitive to docetaxel. Eventually with continued use, the docetaxel-resistant strains take over. That's why it may be important to NOT use it too early: such use may select for resistant strains, which may, paradoxically, increase PC mortality. We don't know enough about all this yet.

- Allen
Posted 9/22/2015 11:26 PM (GMT 0)
Tony,

Any timeframe on additional data about low volume guys?

Why would chemo be different in say a guy that had a few bone Mets vs. A guy that had several bone Mets? One would think it would be effective for both.
Posted 9/22/2015 11:47 PM (GMT 0)
Jerry,

Cancer unfortunately doesn't follow one's reasonable expectations. It is constantly morphing and changing its biochemistry and ecology. The bone and soft-tissue environment changes the cancer, as do drugs we take against it. Docetaxel-sensitive strains may be in the minority in the early environment, but may come to predominate in the poly-metastatic environment. Still later, through selective pressure, it may become docetaxel-insensitive again. Because of the very rapid reproduction rate of the cancer, many genetic changes occur over time, and nearby cells affect one-another. That's why it's so hard to get rid of - it's like trying to shoot a moving target.

- Allen
Posted 9/23/2015 12:17 AM (GMT 0)
So, years ago chemo wasn't used early on in prostate cancer. Fast forward to 2015 and data shows significant benefit to guys with high volume mets.

In breast cancer they use chemo much earlier. For example, my mother in law had surgery, radiation, and chemo right out of the gate (btw-got mammograms every year).

Are we just finding out now with prostate cancer what we've known for quite some time with breast cancer...that earlier might be better?
Posted 9/23/2015 12:48 AM (GMT 0)
Prostate cancer and breast cancer are very different beasts, and one can't generalize from one to the other. While many kinds of chemo are effectively used for breast cancer, so far only docetaxel and cabazitaxel have shown any proven survival benefit for prostate cancer. Docetaxel was only proven in 2004 for use in castrate-resistant PC, which is typically the first use to be tested. CHAARTED began soon after, in 2006, to test docetaxel for metastatic hormone-sensitive PC.

As I tried to explain, it is not necessarily the case that earlier is better. The danger we have to guard against by taking too facile an approach is that earlier use may hasten resistance. So far, we have seen a benefit to using docetaxel as early as multiple mets are discovered in HSPC.
Posted 9/23/2015 12:20 PM (GMT 0)
I was resistant to using chemo early on despite my diagnosis, for all the obvious reasons but after studying the ongoing research from the Chaarted Trial and others I opted to start chemo 17 months after my DX while first line hormone therapy was still effective (my PSA was holding at <0.1). I came to the realization that I didn't want to become passive in my treatment since I have an aggressive disease and just wait for the first line HT to run its course. I had been aggressive in my approach all along so why stop now.
In July I became a patient of Dr. Myers and he also recommended that I start chemo per the Chaarted Trial (Taxotere) in fact he took it a step further and switched the Casodex that I have been taking since Day 1 to Xtandi. After the first round of chemo and a month of Xtandi PSA went from 0.102 to 0.025, I'm hoping the trend continues. Chemo is no picnic, the hope is in the end it will all be worth it.

Ed

Post Edited (Ed-Bar) : 9/23/2015 6:29:09 AM (GMT-6)

Posted 9/23/2015 12:59 PM (GMT 0)
My husband is G9, 12 of 12 cores positive with 4+5, SV+ and two local nodes showing as enlarged on the scans. He was diagnosed late March 2015 and began early chemo in mid May. He just finished his last of 6 chemo sessions last week. Recent scans show shrinkage of nodes and PSA has gone from 11.4 to 8.4 without HT. Although the original plan was to move on to surgery, he will start Lupron soon and then radiation.

Our MO did not insist on HT during the chemo. I think since chemo attack is designed to attack fast growing cells, it makes sense to allow the PC to be somewhat active during the chemo so that the protocol can do its job. It's interesting to me in that within the Chaartered, Stampede and other studies none of them did a control arm with chemo only. All were either chemo+ADT or ADT alone.
Posted 9/23/2015 1:01 PM (GMT 0)
Ed,

Do you/did you have bone Mets and if so..were you considered low volume or high volume (number of sites)?

I seem to be high volume in a different respect...I have several docs, but see Myers as well.

Thanks for your story.
Posted 9/23/2015 1:37 PM (GMT 0)
Jerry,

Yes, high volume bone mets to my spine, pelvis, ribs, sternum and pelvic nodes. This is in my profile - not sure why my signature is not popping up under my posts. One note - part of my aggressive treatment was to have my prostate and some nodes treated with IMRT last fall. Myers said this was a great move - to reduce the tumor burden.

I have several docs too (local medonc who worked with Myers at the NIH, uro, GP, radonc, cardiologist) they are they are my "team" that I've assembled - Myers is now the "head coach" in my case however. Seeing him was like entering a whole new world when it comes to treatment.

Ed
Posted 9/25/2015 6:52 PM (GMT 0)
Hi Tall Allen:

You wrote: "Another potential benefit seen in a recent study is that it may, in some cases, restore sensitivity to Xtandi and/or Zytiga after the cancer has become resistant to those."

Do you have the citation for that Study? Having failed Zytiga and Xtandi, and now in Chemo with Taxotere, I am very interested in where I go next.

Houseboy
Posted 9/25/2015 8:08 PM (GMT 0)
What we learned this year is that an androgen receptor mutation (AR-V7) drives early resistance to Xtandi and Zytiga. The mutation doesn't appear to be stable - some men who are AR-V7 negative become AR-V7 positive after using Xtandi or Zytiga. But it can go the other way too:

Serial Blood-Based Analysis of AR-V7 in Men with Advanced Prostate Cancer

It's only in 14 men, but 6 of them reverted from AR-V7–positive to negative status during treatment with docetaxel or cabazitaxel. I think it seems worth a try to re-challenge after this round of chemo.

- Allen
Posted 9/25/2015 8:17 PM (GMT 0)
Many thanks Allen. I really appreciate (as I am sure we all do ) your dedication to research on PCa and its therapies. Many would never be aware of these jewels of knowledge if it were not for you.

Houseboy
Posted 9/26/2015 12:11 AM (GMT 0)
I agree. Thanks Allen.
Posted 9/26/2015 1:40 AM (GMT 0)
You don't see Provenge mentioned much anymore....My last PSA test a few days ago came back 1.4 so it looks like my 5 year remission is coming to an end..meet with my MO in a few weeks to plan a new course or treatment....As this forum demonstrates, everything is in a state of flux....But it looks like the honeymoon is over....
Posted 9/26/2015 4:20 PM (GMT 0)
It's certainly my pleasure, houseboy and Jerry L.
Posted 9/28/2015 7:47 PM (GMT 0)

Jerry L. said...
Tony,

Any timeframe on additional data about low volume guys?

Why would chemo be different in say a guy that had a few bone Mets vs. A guy that had several bone Mets? One would think it would be effective for both.

Not anytime soon. And possibly not from E3805. That stated I do believe that earlier docetaxel can in fact be more effective than later. I know many of the doctors on that trial agree with that hypothesis. But it's also a consensus among there are dangers of doing more harm than good.

CHAARTED gave us a clear picture for the particular group is was successful in. Through artful selection, guys like your case may in fact be evaluated for early Chemo.

Maha Hussain spoke at PCRI a couple years ago and stated that if we could prevent metastatic skeletal related events (SRE) particularly in the spine that early use is warranted. Her point being that if men have single a plural skeletal lesions but do not quality for E3805 could in fact still be that patient where reduction in SRE will improve quality of life. As it is well known that ones the SRE's occur and cause paralysis it is always irreversible.

Nick Vogelzang has also enrolled men for various reason for earlier use outside of current guidelines for docetaxel use.
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