Does cabazitaxel have targeted potential in late stage prostate cancer?

A research team working just down the street here in Philadelphia thinks cabazitaxel (Jevtana) may have expanded potential in treatment of some men with castration-resistant prostate cancer (CRPC).

Knudsen and colleagues have recently initiated clinical trials based on a hypothesis that cabazitaxel-based chemotherapy might be more effective than docetaxel-based chemotherapy when used sooner in treatment of some men with CRPC. In particular, this may be the case for patients with tumors that no longer express the so-called retinoblastoma (RB) gene, and who have become castration-resistant as a consequence.

The hypothesis itself is based on data in this paper by de Leeuw et al., just published in Clinical Cancer Research. (See also this media release from Thomas Jefferson University.)

Clearly an hypothesis like this, based on laboratory data and animal studies, will need to be tested in actual patients before it can be validated and confirmed. Here is the link to a small Phase II study, currently enrolling up to about 25 patients at several centers, in which treatment with cabazitaxel + abiraterone is being compared to treatment with abiraterone alone in men who are castration resistant and who are also chemotherapy naive and abiraterone naive. If results from this trial appear to be positive, then a larger trial would be necessary to validate the hypothesis.

10 Responses

  1. This totally makes sense! Why not hit it with your best shot? I wish we could participate in this trial but my husband has bone marrow suppression going on. He has just tried the Zytiga and unfortunately it has not shown any signs that it has worked. His current PSA is 6,045. He was on the Zytiga for 7 weeks. Ideas for a treatment going forward? Just to make matters even worse … liver metastasis! … In what you see in a lab setting, is 7 weeks long enough to get a response from this drug?

  2. Sue:

    Not everyone responds to Zytiga but, in my experience, 8-12 weeks is a better period of time in which to determine the effectiveness of the drug. I was nowhere near the PSA level of your husband, but I had liver metastases and an elevated PSA when I started Zytiga. It took 12 weeks before I saw a noticeable drop in my PSA. I have now been on Zytiga for 27 months and it is managing the cancer well (PSA below 1.0).

    I would encourage you to work with your husband’s oncologist to explore every possible treatment option and, if possible, participate in a beneficial trial such as the one described above.

    My best wishes for you both.

  3. Thank you Rob; Dave has bone and CT scans on Monday followed by a oncologist appointmentt on Wednesday. At this time we are basically being pushed to palliative care. Dave is only 64. We live in Canada. I am going to bring the time frame you have mentioned to him.

    Best Wishes to yourself as well

  4. Sue,

    I’m so sorry to read about your husband’s situation. I have a similar situation here at home with my 68-year-old husband.

    He was diagnosed in July 2010 with advanced prostate cancer and was on hormone therapy until summer of 2013. He tried Zytiga; I don’t remember for how long, but it did not seem to help, so with a rising PSA he began chemotherapy (docetaxel). At one point, he switched over to Jevtana, but returned to docetaxel, along with Xtandi.

    We have reached our 5-year “anniversary” of his diagnosis and feel very blessed to have come this far. My husband’s PSA has ranged, over the past 5 years, from “unremarkable” to a high of 93 right before he began chemotherapy. Presently it is on the rise again from under 10 last winter to now in August at 64. Liver metastases were found about 1 year ago.

    We visited Duke University Hospital last October, then M. D. Anderson this past March, and then the University of Alabama in Birmingham in June. My husband didn’t qualify for any of their clinical trials offered. Last week he began receiving home health visits (three times a week) to drain his lungs due to pleural effusions. I’m right there with you asking for any new treatments available.

    I would like to keep in touch since we have similar situations, if you are interested. Also, if any others reading this web site care to share their experiences with me, I would definitely be interested in hearing from you, as well.

  5. Dear Susan, and Sue (and anyone else who is interested):

    If you join our social network and look for the group “Experimental Drug Trials/Prostate Cancer” under the “Groups” heading, it was specifically designed to make it easy for patients and others to talk to each other directly about this sort of topic and share knowledge, and would be a really easy way for you to keep in touch with each other. Communicvations on the social network can also be completely private if you prefer. Even I can’t see the private ones!

  6. Hi.

    Our news just keeps getting worse all the time. The oncologist’s appointment for Dave had the unmistakable, “Sorry, there is nothing else we can do.”

    The bone scans show cancer in long bones (legs and arms) as well as worsening pretty much everywhere else. His PSA on August 12 was 6,045.5; by the 19th it had moved and measured 7,862.2. They pulled Zytiga from treatment as well as pulled Dave off Fragmin because his platelets tanked at 26. Normal low platelets counts are ~ 140. This is a very critical time as we cannot proceed with Jevtana chemotherapy, even though I was able to secure it for Dave.

    Dave was diagnosed in May of 2013 and, from the start of this battle, I have never felt confident or secure in what was being done. I had asked to have him treated with chemotherapy in August of that year thinking we should be hitting this with everything we can but was told Dave with stage 3/4 prostate cancer was not sick enough! You have got to be kidding was what I said. I think the trick to getting the cancer is sequencing of the treatments available. There simply has to be a master plan: something that takes in the genome, stage, and aggressiveness of the cancer. From what I have learned is there are variations to prostate cancer and the outcome for the patient greatly depends on knowing what to use first. I see where now chemotherapy is being used front line, and to me that makes sense.

    I wished I could have persuaded them to use that for Dave because this could and should have been a different story for us.

    Sue Mather

  7. Dear Sue:

    I am very sorry to hear about the continuing progression of Dave’s disease.

    You are right that new data from the CHAARTED and STAMPEDE studies have recently suggested that early combination therapy with ADT + docetaxel-base chemotherapy can have benefits for many men who are initially diagnosed with metastatic prostate cancer. Unfortunately, at the time Dave was diagnosed, all of the available data still suggested that there was no significant survuval benefit at all associated with that type of treatment, so I can understand why the doctors told you that Dave wasn’t sick enough for that, at that time. I should also note that in the CHAARTED and STAMPEDE trials the combination of ADT + docetaxel-based chemotherapy has not been curing these men, although it has delayed the onset of castration-resistant disease by about 12-18 months compared to ADT alone.

    We now know that there are at least a couple of dozen different types of prostate cancer … some are soft and fluffy (“kittens”); others are deadly and swift (“tigers”). Clearly Dave got caught by a tiger. And while you are right in theory about the possible benefits of the appropriate sequencing of some of the new drugs that have come to market, to date there is no known therapy that will actually place any men with aggressive forms of prostate cancer into more than a relatively brief and temporary remission (regardless, as far as we can tell, of the order and combinations in which these drugs are used). We are still “learning as we go”, but we quite certainly aren’t learning enough fast enough for men like your husband — which is a great shame.

    I would like to be able to tell you that I do know of other experimental drugs that might be able to help Dave. Alas, I do not. There are no meaningful clinical trials that I know of that I could tell you he is either eligible for or which would hold out serious hope for a clinical benefit.

    If anyone else has any better ideas, please feel able to chime in.

  8. Sitemaster:

    You are obviously a highly educated man. Why has medicine created such a controversy as far as PSA testing is concerned? They know prostate cancer can have very few symptoms until its to late, yet Task Force guidelines don’t recommend screening. They know three out of 100 men will die the worst death imaginable!

    With blood work some testing always has false results, but we do them anyway. A women’s pap smear can also be inconclusive with false reads. No one ever tells a woman her cancer screening is not recommended. Why are they making a sacrifice out of my husband.

    In 2009 I booked Dave a complete physical, even specifically asked for all PSA and DRE exams to be done. He was 57, heathly, fit, and had not had that screening done previously. His mother had breast cancer; he is a only child; we had no history of his grandfather, and yet he was told, “You are to young to be worried about prostate cancer, it is not recommended to screen for it, and you are not at risk.”

    The following year the same medical practitioner didn’t think there was anything wrong with Dave having ED problems (“All men have that”) or thinking he had diabetes because of frequent urination; still no PSA. The summer of 2010 he said he thought he had arthritis; he just ached. He wouldn’t go in 2011 because of the attitude in 2010.

    In December of 2012 he had to beg her to do PSA testing and again she was hazarding him against it. His PSA that day was 80. She didn’t even know how to read the results and told him it was 8.

    On Wednesday his PSA was 9,153.8 and my husband is dying this horrible death and I can’t find anything to stop it and God only knows I have looked and researched for anything to possibly help. I couldn’t even begin to tell you how every second of every day just how much my heart is breaking. It is a simple blood test that is not written in blood but it sure can be a indicator of something going wrong. Science has so many other ways after screening to identify the tigers from the kitty’s and I think its high time we started to rely on that once we know cancer is in fact being faced. We live in Ontario, Canada, and the physical exam has now been put to 3 years from 1 and that physical is allotted 20 minutes. How much is that patient being educated about prostate cancer?

    When we quit her — before we even knew Dave had incurable stage IV cancer — I asked her why she wouldn’t you do screening for Dave. Her answer, “He LOOKED HEALTHY!”

  9. Dear Sue:

    There is an old story that most nurses know well. It goes like this: “What do you call someone who graduated last in his class at medical school?” … The answer, of course, is “Doctor.”

    It seems very apparent that the doctor that Dave was seeing from 2009 until 2012 was not very good at her job. She would not have been helped by the fact that we now pump out information about medical issues at a rate that defies intake for every primary care doctor in the world.

    I am lucky. I have an excellent primary care physician at an excellent institution, but even he has made it very clear to me that it is impossible to keep up to date any more. He just has to do the best he can. The other thing is that even when one has information, applying it wisely (“knowledge”) is a whole other matter.

    The controversy about PSA testing has a 35-year history that has been riddled with over-emphasis on its value by some and crass resistance to its use by others. The wise will tell you that there are really good ways to use PSA testing that can minimize its inappropriate use and maximize its utility. The same is true of things like mammography.

    I am sorry about what has happened to Dave. He definitely got the short end of the stick. And we will never know now whether — if he’d had that PSA test back in 2009 — he might have been found to have a curable form of prostate cancer. Your anguish over this series of events is entirely justified and understandable.

    If there is a lesson for others in your and Dave’s experience it is this. Do not assume that all doctors are good doctors. Many doctors never learn to really “listen” to their patients; they just hear what the patients say but do whatever they were going to do anyway. Finding a good doctor takes work, but finding a good primary care doctor is at least as important as finding a good grocery store or a good plumber — and we all know how important that can be.

  10. Sue Mathers:

    Although “each situation is different”, which we hear repeatedly, I grieve along with you regarding the “but what ifs”.

    My husband, whom I wrote to you about previously, had an increase of his PSA from 2.0 in December 2009 to 3.5 in Aug. 2010. The primary care doctor’s P.A. read the results and did nothing! No referral to a urologist; no repeat of PSA within one month or so; no prescription in case this was prostatitis; absolutely nothing. This was not the first time my husband’s PSA had a sharp increase. A few years before that, a similar increase was noticed, and nothing was done. This may sound irrational, but I actually am looking into a malpractice suit. Due to the timeframe, there’s a possibility that nothing can be done, but I am pursuing this.

    My heart breaks for you and Dave, as my heart is broken for my husband and me. There must be some means of action to hold doctors more accountable. The lack of follow-up and supervision our primary care doctor had with his P.A. angers me beyond words! As I see it, Sue, both of our dear husbands are dying unnecessarily due to the incompetence of their doctors.

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