Tag Archives: docetaxel

Prostate cancer advances – The Oscars are in…


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I have been attending the ASCO led GU oncology symposium for the last 48 hours. As usual, it is somewhat of a “firehose to take a drink” scenario with great presentations, more posters than you can possibly absorb, and lots of progress on many fronts. I remember when there were only about 50 “GU oncologists” 30 years ago, and about 300 attended this meeting when it first started. The attendance is 2900 from around the world. As one of my patients likes to put on his blog, “help is on the way”, which is really encouraging. There is more to report than I can possibly do in a blog, so I will just poach from existing internet info and highlight some of the existing posts.

Chemotherapy for newly diagnosed patients with many metastases is now the “standard of care” following the CHAARTED trial that I previously discussed. The French completed a smaller study that did NOT show an advantage for using docetaxel “up front”. There are a number of possible explanations that you can read about here. Not mentioned in that discussion is a moderately complex explanation that came up in the discussion period after the presentation. It turns out that ADT leads to changes in the way docetaxel is metabolized. Thus, the approval of the use of docetaxel in the setting of castrate resistant pca (which has been the usual situation) is different from using docetaxel when a patient hasn’t been on ADT for very long. The French study had more toxicity, and potentially more delays in treatment but the relationship of when the ADT started may have been different from the CHAARTED trial and could explain differences. Nevertheless, CHAARTED was larger and I think the trial still sets a new standard.

The optimal duration of ADT when given to enhance radiation was covered extensively by Anthony D’amico. The details are pretty complex, and if you want to wade into these weeds, you can start with his JCO article. Basically, the issue is this: ADT helps radiation therapy be more effective. But it is clearly “toxic” in terms of quality of life, and possibly increases cardiac events in men with a history of heart disease. Both of these factors make it questionable to use at all in men with “low intermediate risk” disease, and we would certainly like to use for as little time as necessary to get the benefit so that quality of life is preserved. In the higher risk patients there is no doubt that it should be used, but the duration is still up for discussion, with the existing “definitive” study showing 36 months is better than 6 months. Generally in such patients, I go over this, and then say, “let’s see how well you tolerate ADT before we reach any final decision on how long to continue”. Certainly a minimum of 4 months is required, and possibly the longer the better, but I suspect 36 months is too long. And really no one has taken into account the factor that a single 3 month leuprolide injection can result in quite variable overall duration of testosterone suppression with older men generally not recovering as quickly as the younger guys.

On the vaccine front, data were presented on Prostvac in combination with the immune checkpoint inhibitor, ipilumimab. The exciting findings in using checkpoint inhibitors (including the PD1 and PDL1 drugs in other diseases has lagged somewhat in prostate cancer because it isn’t clear that the ongoing immune response is very good. (For example ipi alone in prostate cancer didn’t work) However, given the promising data on using Prostvac in the phase II trials, the phase III trial has now accrued all of its patients and we await the result. Meanwhile, investigators have begun to look at whether adding a checkpoint inhibitor to a vaccine can make further headway. An abstract presented at the meeting reported on the early results of this approach. Dr. Singh from the NCI GU oncology team stated “In a Phase 1 combination study of 30 mCRPC patients with similar baseline characteristics (predicted median OS of 18.5 months), patients were treated with PROSTVAC plus escalating doses of ipilimumab. The observed median OS was 31.3 months for all dose cohorts and 37.2 months for patients treated at 10 mg/kg based on updated overall survival data. Furthermore, there appears to be a tail on the curve with approximately 20% of patients at 10 mg/kg alive at 80 months.” This certainly means that if the Phase III trial of Prostvac leads to approval by the FDA, there will quickly be more studies of how to make this vaccine even more effective.

Many of us have been talking at this meeting and other recent meetings about a “kitchen sink” approach combining all of the newer drugs to get a biochemical complete response in metastatic patients and then using a vaccine to “clean up” the microscopic disease that is clearly left behind. I’m looking forward to these trials which are probably a year or two away, but optimism abounds. Example: A new man with metastatic disease who had prostate radiation or surgery 5 years ago is found because of a rising PSA. We do fancy scans with C-11 acetate or choline, radiate the known disease, treat with second generation ADT plus docetaxel x 6, then use the vaccine with a checkpoint inhibitor. (read that link by the way – terrific) Given that prostate cancer is generally a “slow cancer”, there are many men alive today with lurking metastases that will only become apparent 5 or 10 years from now. These guys will almost certainly be able to take advantage of such an approach – never fast enough, but never more promising prospects, either.

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Practice changing results….chemotherapy up front.


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Adding 6 cycles of docetaxel at the outset of hormonal therapy for prostate cancer has been shown to improve survival, especially in men with a high burden of disease. The much anticipated report was presented in detail today at the ASCO annual meeting. Those of you who have followed this blog will remember that I previously highlighted the CHAARTED trial when the trial was stopped prematurely because of the positive result.

The first author, Chris Sweeney, is a good friend and led the study in which several of our patients here in Denver were participants. Thanks guys !

This study randomized 790 men who presented with metastatic prostate cancer and who had never received hormone therapy (ADT) to receive ADT alone (393) vs ADT plus chemothrapy with docetaxel (397) starting up front at the time the ADT was started.  In patients with high volume disease, defined as those men with visceral metastases or >3 skeletal mets including one beyond the pelvis and spine, there was an improvement of 17 months in overall survival from 33 months to 49 months with a p value of <.0006 for significance between the two arms of the trial. The men with lower volume of metastases are also doing better, but the curves for the two treatment arms have not met significance. There was reasonable balance in age, race, psa values, etcetera between the arms. A key point is that 3/4 of the men initially treated with ADT alone went on to receive docetaxel at the time of progressive disease, meaning that this trial can reasonably be considered to reflect a “pay me now or pay me later” with docetaxel toxicity, and the men who were on the “pay me now” arm had the most benefit from the toxicity of the chemotherapy. There was good balance between the arms in terms of the number of men who received others of the newer treatments (abiraterone, enzalutamide, sipuleucel-T).

For prostate cancer, this is akin to the studies of using chemotherapy “up front” in the adjuvant setting that really got medical oncology going in the early 1970’s in women with breast cancer. It opens the door to the study of using aggressive multimodality treatment including the newer hormonal agents, and possibly vaccines, in men with high risk disease at the very outset of their therapy, which should be the next studies. The problems with designing such studies is the very long period of time it takes to get answers. CHAARTED was opened in 2006 and only now, 8 years later, do we have a result. The time could be dramatically shortened if more men would be placed on clinical trials. 1000’s of men were treated with same old same old treatment during the time we worked on CHAARTED. If 50% of them would have been put on this trial in the first two years, we could have had this result about 4 years earlier. Since that takes a major change in how medicine is practiced in the US, don’t hold your breath.

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