ADT + Chemo vs ADT followed by Chemo

EDIT: Please read the replies to my posting below. After I posted it some other members posted important caveats and additional information. - Alan

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The following article in the New England Journal of Medicine reports on a randomized trial of ADT vs. ADT + Chemotherapy for men who are NOT castration resistant.

nejm.org/doi/full/10.1056/N...

If I understand the article, it found that time to progression and overall survival were both significantly longer in the dual therapy group. This was true in spite of the fact that most of the ADT only men were later treated with chemo once they became castration resistant, and many had abiraterone or enzalutamide. In other words, early chemo combined with ADT worked better than late chemo after ADT had stopped working. The average overall survival improvement was 13.6 months, a pretty useful amount of time and much higher than the principal trial on which chemotherapy was approved that found a survival benefit averaging only 2.5 months when given to castration resistant patients.

Interestingly, the greatest improvements were seen with men with higher disease burden (known mets at the time of treatment) than men with lower disease burdens, who did almost as well on ADT alone, though it looks like both groups had some benefit.

So, for those who are on ADT or see it in your future, it's something to discuss with your oncologist.

Alan

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  • Thanks Alan, very timely for me.

  • Chemo is a piece of cake, side effects are highly over rated. The worst thing that happened to me is the hair on my arm pits never grew back. Now when I raise my arms the cops start laughing.

  • Thank you, by providing this link, you have done a service to the community.

    Rich

  • This is the Sweeney team announcing the results of the "chaarted" trial, in August 2015. (The official publication in NEJM.) This article "allowed" cancer centers (at least Roswell Park) to change the standard of care for newly diagnosed metastatic cancer patients. It reports improvements for "high volume" patients, and reached no conclusion for the others (because - I think - lower volume entered the trial later, and by the end of the trial, for them 5 years in, the "low volume" patients were doing about the same, so who knows. The accompanying graph seems to show a difference.)

    "High volume" is defined in the study, but is less than clear. Bone mets in the spine and pelvis did not qualify. Other sites (arm, leg, rib, skull) would.

  • That finding changed the mindset of practicing oncologists everywhere. According to my reading and my personal sampling, they seem to have embraced it hook, line, and sinker. Reality checks in the form of closer inspection, however, reveal important details many oncologists are overlooking. Those details (plus the first of several books I'm reading on the depth, duration, and likelihood of chemotherapy's devastating side effects) transported me from hot to trot to Show Me The Money.

    1. Two similar studies differ very significantly, one to the point of finding no advantage.

    2. Its cohorts are narrowly defined. Some analyses of the three studies claim that biases the outcomes significantly.

    3. The study's very impressive findings, especially its 17-month advantage to early chemo, is expressly limited to cases of lung, liver, and/or bone mets ... all preloaded with short survival and nasty morbidity/toxicity to begin with.

    4. In lesser cases, the benefits drop back to 12, 10, even 6 months even in this most optimistic of early chemo studies ... not a big payoff if the entire added time is totally wracked with the SEs which MOST chemo pts reportedly encounter. We're still talking about added months, not the curative potential breast cancer pts may see.

    5. And, oh yes ... early chemo's advantages apply only to men < 70 years old.

    6. Then there's the little matter of studies showing similar benefit from a MUCH less onerous OTC drug, Celebrex (it's been exonerated of its heart attack problem rumor.)

    7. And is prednisone, with its own independent nasty SEs, necessary with chemo? Yale Med says no.

    I realize my comments here omit a great deal of detail, most notably Who Sez? (These concerns and caveats did not originate with me; they come from other published trials and from erudite published analyses of this study, backed up by close inspection.) They will have to be added later, after I can get one of the med oncs to back up his high level of urgency with action in the form a needle into my belly concurrent with some answers to a few highly relevant questions such as when to begin prophylactic gynecomastia measures and whether to get baseline PSA and DEXA tests. It is taking weeks at a time to even get a callback despite their sky-is-falling one-month deadlines back in mid-December. My usual providers, including a very popular and busy integrative radiation oncologist, answer emails within hours.

  • Alan and all others. Just one minor but important "correction". The article reports a MEDIAN increase in survival of 13.6 mo. That means 50% of the men on the combo lived 13.6 mo OR LONGER. That is considered better than "average".

    herb s

  • Don't forget that the MEDIAN number is NOT the average - it is the numbert in the exact middle of all of the number - if there are 51 numbers the MEDIAN would be the number that has 25 below it and 26 above it. The average can be a very different number.

  • I meant to write 25 above and 25 below - my typing is trying at times!

  • My thanks to Martin, Its_Baaaack, and Herb for the corrections and amplifications.

    This stuff is all so complicated and the science so unsettled that it's hard to make any unequivocal statements about prostate cancer treatment.

    Alan

  • My father and so many seem so set on this therapy, and the study, at lest to me, doesn't prove enough benefit but that is yet to see. I see his quality of life going down and cam we really give a median survival and take the individuality of the person, and the cancer out of the picture?

  • I went through the STAMPEDE/CHAARTED trials and I'm glad I did. Started out with lymph nodes the size of beach balls, mets in my spine and hips, on and on. Oh, psa was 850. An Internationally renowned clinical researcher, Maha H. Hussain, MD, urged me to go through with it. So I did. 2 years later, psa 0.07, lymph nodes normal, mets running for their lives. I plan on being around when a kid who is presently in high school is elected president of the United States.

  • I always love to hear about great responses to treatment. It's very encouraging to folks who need to have some hope.

    I also love to hear about guys who participated in clinical trials - which benefit everyone, not just the patients in the trials.

    Alan

  • Your response is better than mine is, with similar treatment, and you started worse. Hrumph.

  • True but, We play the same sport, I'm starting the all star game, you made the team as a backup.Bottom line, we are both doing great!

  • martingugino wrote:

    "Your response is better than mine is, with similar treatment, and you started worse."

    One theory is that chemo is most effective against the most aggressive cancers. If it only harms dividing cells, then if the percentage of cells undergoing cell division / mitosis is high while the chemicals are in the blood stream, more tumor cells will be killed than if the percentage is lower.

    I think that's a great thing because ADT and immunotherapy seem most effective against lower risk cancers. Chemo gives patients at the other end of the risk scale a chance that they might not get with other treatments.

    Alan

  • Ty for this, I'm discouraged often by my dad's weakness pale mess etc rt now but the psa is falling though slowly . I needed to hear your words today. In fact I'm going to get off line on that high note. Thanks and let us know when your son is running because we know he has values and true strength he's learning from you

  • Re:" I plan on being around when a kid who is presently in high school is elected president of the United States."

    That could be next year. Stranger things have happened.. :)

  • I'm doing the early chemo with ADT on my second cycle right now. So far the SEs are tolerable and worth even a few more months as long as they are good quality. I figured I would probably end up doing chemo anyway after my PCa became castrate resistant and my options started to dwindle. So why not do it now? I decided that it would make more sense to just do it up front, especially if there is even a potentially bigger benefit. I also figured I would regret not doing it up front if my time to resistance ends up being shorter than the average. I would always be wondering if I could have gotten longer with chemo. This way, there will be no need to wonder if not doing chemo was a mistake. I have more peace of mind knowing I'm throwing everything at it that I can right now. Of course there are no guarantees for any of us, but so far my response has been good so I can't complain. PSA went from 400 to .6 in 2 months and Alk Phos from over 600 to 187.

  • It sounds like the treatment is working great. Best of luck with it.

    Alan

  • Hi gregg57

    How is it all going my Oncologist is thinking I should also have ADT + Chemo my PSA is aggressive but no evidence on bone or lymph nodes yet, basically they don't know where it is.

    I can only hope it works for me i guess.

    Cheers

    Gary

  • It's going really well for me, just posted about my progress. PSA is now .2 !!!

    My feeling is that the more you throw at it early, the less of it there is to get you later. Kick it while it's down and kick it hard! Stamp it out early if you can. It's like a fighting a fire. The smaller it is, the easier it is to put out.

    As far as chemo goes, it's not as useful if done late in the game because it's not very powerful. The dose has to be limited in order to keep the damage to your healthy cells down to what your body can tolerate.

    A large part of why chemo works is the slower recovery time of the cancer vs the rest of your body which helps amplify the power of the chemo. The cancer recovers more slowly so with each cycle of chemo, the cancer goes down a little more.

  • Thanks for the quick reply gregg57 ive also started a new thread just in case as my Oncologist will be letting me know if i can have the chemo on Monday or Tuesday.

    Hope you keep on kicking it.

    Cheers

    Gary

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