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How long does it take Lupron to kill cancer?

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Posted 7/2/2015 1:07 AM (GMT 0)
My RO says I have microscopic cancer cells in my pelvis that did not show up on scans. But the Lupron will kill it. I forgot to ask her how long it takes. Anyone know how long?

Thanks
Tom
Posted 7/2/2015 1:50 AM (GMT 0)
Your RO made an optimistic statement. If you have a variety of PCa that cannot morph into one that can make its own T, or learn to live on something else, it will take the time that the Lupron to cut your T to castrate levels, then the time it takes the cells to die off.

Understand that Lupron does not "kill" PCa cells. Some will argue with me on this, but the effect is gradual, not immediate. It removes their source of food, which causes them to either starve to death, or evolve into using something else for food.

Your PSA should start dropping about the time your T gets to near-zero levels, and continue to drop.

That happened for me in the first couple of years, but that tiny bit that survived now grows without T.

You are in a twilight zone of sorts. Your RO may be right. But maybe not. Regardless, it will take time, and time is what gives them the opportunity to push out the next med.
Posted 7/2/2015 1:52 AM (GMT 0)
He is expressing a hope. It certainly makes the cancer more amenable to radiation/immune-induced killing. It won't kill all the cancer on its own, unfortunately, only along with radiation. It seems to take longer, the higher the grade of the cancer. Best guesses are anywhere from 6 months to as high as 3 years, depending on how impervious it is to radiation.
Posted 7/2/2015 2:53 PM (GMT 0)
Tom,

The Lupron doesn't kill cancer all by itself but when you add Lupron to radiation treatments the combination kills cancer better than the radiation would do by itself. What she was probably talking about was that with your Gleason 4+3 cancer you are in a sort of a higher risk category for the cancer coming back. This happens because that sort of cancer tends to spread to other tissues because of those microscopic cells outside the prostate that sometimes don't get quite enough radiation to kill them. They will be giving your prostate enough radiation to kill all the cancer there so that's not a problem. They will probably give the surrounding tissues a bit of a zap, too, but they can't just cook a man from the navel down so that dose is lower and the Lupron will help any microscopic cells in the area to die from the radiation.

How long that takes is hard to answer. The longer they keep you on the Lupron the more likely it is to work but Lupron has side effects that nobody likes and, depending on your risk category, you get into diminishing returns after a while.

I was a Gleason 9 so my doctors kept me on Lupron for two very long years. You might get off with a shorter sentence since your risk as a Gleason 7 is one notch down.
Posted 7/2/2015 4:35 PM (GMT 0)

PeterDisAbelard. said...
Tom,
Lupron has side effects that nobody likes

This is why I'm asking. Thanks for the feedback.
Posted 7/2/2015 6:17 PM (GMT 0)

The intention here is not starting an argument about the mechanism of androgen deprivation on prostate cancer cells. First it is important to know that not all prostate cells are androgen dependent. Most prostate cells depend on androgen to survive and to maintain the gland operational(new cells are born while others die). When deprived of androgens, androgen dependent cells undergo a programed death. This does not mean all cells die at once. The main cell death process mechanisms are apoptosis, necrosis, autophagy and necroptosis. Androgen deprivation also causes a reduction of blood flow to the gland that is reported as the cause of massive cell death.

The point here is to correct the notion that androgen deprivation itself is not the direct cause of cell death. There is ample medical evidence that it is. Androgen deprivation weakens and sensitize cells to radiotherapy. This have been proven by improved survival of patients treated with this combination treatment.

There is an interesting paper by Isaacs et al about PCa cell origen and the process of androgen independence. Take the time to read it:

Arnold JT, Isaacs JT. Mechanisms involved in the progression of androgen-independent prostate cancers: it is not only the cancer cell's fault. Endocr Relat Cancer. 2002 Mar;9(1):61-73. Review. PubMed PMID: 11914183; PubMed Central PMCID: PMC4124629.

Posted 7/3/2015 11:59 AM (GMT 0)

ralfinaz said...
The intention here is not starting an argument about the mechanism of androgen deprivation on prostate cancer cells. First it is important to know that not all prostate cells are androgen dependent. Most prostate cells depend on androgen to survive and to maintain the gland operational(new cells are born while others die). When deprived of androgens, androgen dependent cells undergo a programed death. This does not mean all cells die at once. The main cell death process mechanisms are apoptosis, necrosis, autophagy and necroptosis. Androgen deprivation also causes a reduction of blood flow to the gland that is reported as the cause of massive cell death.

The point here is to correct the notion that androgen deprivation itself is not the direct cause of cell death. There is ample medical evidence that it is. Androgen deprivation weakens and sensitize cells to radiotherapy. This have been proven by improved survival of patients treated with this combination treatment.

There is an interesting paper by Isaacs et al about PCa cell origen and the process of androgen independence. Take the time to read it:

Arnold JT, Isaacs JT. Mechanisms involved in the progression of androgen-independent prostate cancers: it is not only the cancer cell's fault. Endocr Relat Cancer. 2002 Mar;9(1):61-73. Review. PubMed PMID: 11914183; PubMed Central PMCID: PMC4124629.

Good info. Thanks!
Posted 7/3/2015 12:09 PM (GMT 0)

Tall Allen said...
He is expressing a hope. It certainly makes the cancer more amenable to radiation/immune-induced killing. It won't kill all the cancer on its own, unfortunately, only along with radiation. It seems to take longer, the higher the grade of the cancer. Best guesses are anywhere from 6 months to as high as 3 years, depending on how impervious it is to radiation.

Hey, Tall one. This topic keeps cycling around, and since I'm at a decision point whether or not to continue Lupron for my full 3 year sentence it's of great interest.

Have you seen anything newer than Dr. Nabid's last ASCO presentation about duration of ADT? The grade of cancer (mine's 5+4), linking to HT duration, has been a very elusive correlation to find.

I'm increasingly thinking of requesting no more Lupron shots. This will leave me with having had 28 months on active treatment. I'm due for the next one toward the end of July, and I think I'm going to refuse it. My wife thinks I should stay the course, but I'm just thinking the remaining benefits aren't worth the ever increasing side effect burden...

Jerry
Posted 7/3/2015 3:51 PM (GMT 0)
ralfinaz interesting reading - thank you. Best wishes and Happy 4th (if you celebrate).
Posted 7/3/2015 3:54 PM (GMT 0)
goatts I don't know much about prostate cancer but maybe the word "suppress" is better than "kill"? Don't know.

I do think you're on a good treatment path.
Posted 7/3/2015 8:17 PM (GMT 0)

Hi Jerry,

You are right that in cases with high risk/high grade disease as yours there is little research supported by RCTs to give you a guideline on how long to stay on ADT . That said, intermittent ADT has demonstrated equivalent survival benefit as continuous deprivation.

This means that you could stop ADT and closely monitor your testosterone rebound with little risk. Close monitoring will be required. Baseline testosterone and DHT would be good to know. Monitor PSA closely while monitoring the normalization of testosterone. As this happens your QOL would improve and the proper effect of your IMRT treatment will be exposed. Based on your PSA response after the combination treatment there is a good chance that this combination treatment has done the job.

There is a recent article based on nomograms that you might find helpful. The full paper is free and available on PubMed:

Stoyanova R, Pahlajani NH, Egleston BL, Buyyounouski MK, Chen DY, Horwitz EM, Pollack A. The impact of dose-escalated radiotherapy plus androgen deprivation for prostate cancer using 2 linked nomograms. Cancer. 2013 Mar 1;119(5):1080-8. doi: 10.1002/cncr.27857. Epub 2012 Oct 23. PubMed PMID: 23096533; PubMed Central PMCID: PMC4347814.

RalphV

Buddy Blank, I do honor and celebrate our Independence Day!

BTW, kill is the right mechanism.

Posted 7/3/2015 10:13 PM (GMT 0)
Jerry,

The Nabid study is the most definitive RCT we have to date, and I haven't seen it in a peer-reviewed publication yet for fuller details. Certainly, judgment plays a role. So if you have multiple high risk factors, you might consider longer ADT. He also showed that quality of life is improved by the shorter treatment, which isn't surprising.

- Allen

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Posted 7/3/2015 10:17 PM (GMT 0)
ralfinaz,

Intermittent ADT is never used in conjunction with RT+adjuvant ADT. It's only used in non-curative protocols.
- Allen
Posted 7/4/2015 12:02 AM (GMT 0)
Hey Goatts,
I can't tell you how long but I can give you some personal experience. Before I started lupron and casodex my PSA was 240 and my biopsy indicated that my prostate size was 61 grams with 11 of 12 cores positive comprising over 90% of the sampled cores. There were two hot spots in my spine. I began hormone therapy on 12/17/2013 and my surgery was performed on 2/19/2014. The final path showed a prostate of less than 31 grams and my tumor comprising only 6% of my prostate. A later bone scan showed that the two hot spots had resolved. To date they have not returned. There is more to this story but I won't bore you with that. The point Iam trying to make is that it can work very fast but the results are different for everyone.
Posted 7/4/2015 12:46 AM (GMT 0)

Buddy Blank said...
goatts I don't know much about prostate cancer but maybe the word "suppress" is better than "kill"? Don't know.

I do think you're on a good treatment path.

The RO actually used the word "kill". This was during a very short discussion with me bombarding her with questions about a massively complex malady. I've talked to 3 RO's that all say it's definitely microscopically in my pelvis even though the scans don't show it. She thinks there's a good chance that the Lupron can kill it. The Lupron will suppress the large tumor in my prostate and make it vulnerable to the radiation. I didn't think to ask how long that's why I asked the question here. I'll ask the doctor next Wednesday.

Thanks
Posted 7/4/2015 1:40 AM (GMT 0)
I draw a very thin line based on years of having been nit-picked in technical discussions.

To "kill" is to immediately remove life. A sniper kills a target. To provide the circumstances that lead to eventual death from starvation is to "cause the death of".

One is "one round, one kill" the other is everything else.

The end result is the same, the procedure to arrive at that end, very different.
Posted 7/4/2015 2:58 AM (GMT 0)

Allen,

One of Jerry's options if he stops adjuvant ADT at this point and there is biochemical failure is to restart ADT to prevent progression. There have been a couple of trials that demostrated QOL benefits when patients adopt IADT as compared to continuous ADT in this setting. Given his excellent results his risk should be minimun and he would then know the combined result of his treatment.

RalphV

Posted 7/4/2015 5:04 AM (GMT 0)
Redwing, after 28 months on Lupron, it will take you body a LONG time to recover if it EVER recovers....So knocking off the Lupron a little early will not make that much difference...You could meet half-way and just get a 3 month shot...
Posted 7/4/2015 6:09 AM (GMT 0)
ralfinaz,
Perhaps you can point me to a trial where ADT was stopped and restarted as part of the adjunctive treatment after definitive radiation because I have never seen one like that, and if there is one, I would like to see it. What I have learned is this: either it was curative or it wasn't. If it wasn't, one is then put on lifelong ADT, either continuous or intermittent. We almost always approach treatment for the cure first. What Jerry is struggling with is whether his ADT has been of long enough duration to cure him.
- Allen
Posted 7/4/2015 6:52 PM (GMT 0)

Allen,

If the correct time of adjunct ADT to RT remains unknown to effect a "cure" why would a randomized trial involving adjunct IADT to RT be available? On the other hand, IADT has been tried on RT monotherapy that did not "cure"...

Jerry said: "I'm increasingly thinking of requesting no more Lupron shots. This will leave me with having had 28 months on active treatment. I'm due for the next one toward the end of July, and I think I'm going to refuse it. My wife thinks I should stay the course, but I'm just thinking the remaining benefits aren't worth the ever increasing side effect burden..."

To that I mentioned that his option might not be much of a risk and he could always restart ADT without any detriment to his current treatment result. I was kind of supporting his thoughts given the lack of RTC support to decide when to end ADT in his case. After all his combination treatment result at 28 months is excellent except for the side effect burden.

RalphV 

Posted 7/6/2015 1:40 AM (GMT 0)
Thanks for all the comments, guys! It is something of a dilemma, with few real answers. I get both of your positions. Ralph, you're echoing my thoughts, and something I brought up last time with my MO. Their concern was that since I'm still in primary treatment, they don't want to give the cancer a chance at all to gain any ground by stopping early.

To me, it seems after this long that if my PSA does bounce up now beyond 2 after stopping ADT , then the whole RT+ADT is a fail and long term ADT is needed anyway.

I suppose the question may be how long does it take for ADT to have its greatest killing/starvation effect on the bad cells, after RT. No point continuing further if it's just having a suppression effect at this point.
Posted 7/6/2015 2:13 PM (GMT 0)
Without taking any particular side in Jerry's discussion I have to admit that I find Ralph's introduction of the concept of intermittent ADT to be an irrelevancy. I can't see how it is different from simply deciding to cut the 3-year concurrent ADT period short and watching the PSA to see if it has to be restarted because the curative attempt has failed.

As for the question of "how long ...it [takes] for ADT to have its greatest killing/starvation effect on the bad cells, after RT" I think that taking the question narrowly -- simply in terms of killing off the remaining cells -- there is no actual maximum. There is a limit that is approached asymptotically over time. The argument then is not that the third year gives no benefit but that the benefit is small and not worth the side effects is has to be weighed against.

I've had similar discussions with my RO and have yet to win an argument. I tried to sell him on stopping at 18 months instead of 24 and, more recently when I became impatient with the pace of my recovery, I tried to sell him on drugs that speed up the process. We had that second argument 9 months after my ADT had worn off and my total T had only recovered to slightly over 100 ng/dl. We agreed to wait to see what it had done in another three months. That three-month check was last week. I am up to 195. He said, "See, it's almost doubled in three months." My take was that it had gone up only 30 ng/dl a month which left me another year away from my pre-ADT baseline (less 10% for being four years older). No sale. Sigh.
Posted 7/6/2015 2:48 PM (GMT 0)

Hi Peter,

If Jerry would decide to stop his present course of ADT and experience a PSA surge don't you think it is important to know that intermittent ADT has yielded similar results as continuos ADT? This with the added benefit to have reduced SEs and a more exact knowledge of his current treatment efficacy. That was the intended relevancy.

There is certain degree of risk of doing this in a patient with poorly differentiated disease, but closely monitoring testosterone, DHT, E2 and PSA one can reduce that risk to an acceptable level. More so in a patient like Jerry who has had an undetectable PSA for his current treatment period.

RalphV

Posted 7/6/2015 5:32 PM (GMT 0)
PDA -

I'm glad that those testicular cells are waking up, however slowly. We'll have to watch the "wake-up" curve to see if it's linear or geometric. But these things seldom follow nice mathematical models as we would like them to.

My theory about why "18 months is as good as 3 years" is that the curative agent is not just ADT, but is ADT with RT and the immune system. I believe that at first, the immune system is activated by the all the dead bits of cancer cell surface antigens floating around after the initial phase of gross killing by ADT+RT. Then, while the ADT suppresses cancer growth and kills some with diminishing efficacy (asymptotically, as you say), the immune system hunts down and kills any remaining cancer cells it finds, hopefully completely. Then the immune system (Tregs) unfortunately begins to recognize cancer cells as "self" and becomes inactive at any further killing. That seems to have occurred by 18 months, and it may vary somewhat with the individual, but it always does shut itself off eventually. That's why the checkpoint blockers like Ipi and PD-1 are so promising - they keep the immune system active at killing the cancer.

I agree that intermittent is irrelevant at this point. It is not even clear that there is any benefit in beginning lifelong androgen suppression immediately after the failure of salvage radiation.

- Allen
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