Docetaxel Chemo for new metastatic cases ~ beneficial earlier than later.

Good article. I am currently considering a recommendation to do chemo after rising PSA and nodules in CT scan of lung. Bone scan was clear. I am waiting on a lung biopsy to identify the cause of the nodules. Contact with Shands says only 10% or less of metastasis of PCa is to the lungs before the bones.

Tony, thanks for posting useful infomation.

Don

Thanks for posting this, Tony. Makes me feel better. Over 2 years ago, I reported that my own oncologist talked to me about, in my unique case (not a general usage), of possibly using Taxotere as a first advanced treatment for me when the time comes. Many here ridiculed the suggestion, pushing for the more normal approach of HT. He said there are cases, where the chemo can shock the cancer, and he had similar success with difficult BC cases using the same approach.

Just find it interesting how all these treatment choices evolve over time. In a recent letter from my doctor to the VA, he even included this possible chemo route as the next possible treatment for me when it's the appropriate time.

Good information here.

David

Keeping Faith,
Tell Dan Petrylak I said hi. He's a great guy! (He'll remember I am the PCa patient advocate at SWOG)

Haha, I'll be on a conference call with him later today. He leads quite a few trials at SWOG.

Tony

Post Edited (TC-LasVegas) : 12/9/2013 11:05:27 AM (GMT-7)

Jim,
There are quite a few trials that are for early high risk with mets and with rising PSA. Many centered around early Provenge, Enzalutamide, or Abiraterone ~ or any combination of the three. But also early chemo, like this one, and new agents like ARN509.

The best thing to do is talk to your doctor about them. And if he does not have any to recommend then maybe get another opinion at a major institution. UF Shands is an ACRIN center so they should have quite a bit of options for you. One I am working on right now is S1216 for SWOG. Very similar approach ~ one arm is ADT (LHRH+Bicalutamide) versus ADT+TAK700. Here is that one:

clinicaltrials.gov/show/NCT01809691

Tony

Tony,
I don’t think that the results from this study are ”game changing“ or “practice-changing” as said by the lead investigator Christopher Sweeney. The problems are the unclear pre study therapies. Some Pts. might have had Surgery, RT or ADT (>12 Month ago), and have developed metastatic disease further on. But even at the start of the trial the patients are allowed to have ADT for less than 120 days, 4 Month! They must have Visceral metastases (extranodal) or at least 4 bone lesions, with one must be outside of the vertebral column or pelvis, and received an ADT1 which is quite insufficient in this setting, and usually will be combined with an antiandrogene like Bicalutamide and some bisphosphonates or RANKL inhibitors.
 
This setting is very unusual in primary diagnostics. 3-year overall survival for patients with a high extent of metastatic disease was 69%/52.5% - very low as we know that even in metastatic settings people do live quite a long time nowadays.

The French/Belgium GETUG-AFU 15 study with androgen-sensitive but metastatic PCA patients using ADT2 +/- Docetaxel show no benefit in survival:

“Docetaxel should not be used as part of first-line treatment for patients with non-castrate, metastatic prostate cancer”

So, what do we learn out of this? Using first-line Docetaxel have some beneficial effect in very heavily metastatic patients only – and this is nothing new!

And I'll add that anything which changes the order of treatment that insurance companies will cover is certainly important to the patient community. Those changes happen because of acceptance in the medical community and evidence that the treatment has value.

As I discovered, it did not matter what my uro & oncologist wanted me to do based on my situation, it was what the insurance would cover as standard practice.

Haha,
To be certain that something is changing ~ I have just been contacted this morning to take part in two "emergency" calls at SWOG to go over the impact of the CHAARTED trial on current trials we are running. We are working in co-operation with ECOG-ACRIN. In my two years here this is a first. Stay tuned for the news.

The reasoning for this is that there is a significant population of men in these trials that should probably be moved to chemo. Or even there is a significant number of future men that should not be recruited as the trials are written because chemo is quite possibly a better survival rout in their cases.

Tony

Hard to say WW,
If I was in your hubby's shoes I would likely have considered this trial though. In fact I did agree to join early on a trial with Taxotere in two of four arms but got denied by clerical error. But that was 7 years ago and that trial died because of enrollment issues. It was since revived with new parameters but by that time I was already doing HT and radiation after RP.

In the CHAARTED trial, your hubby is a borderline case. He had n-mets and also had local mets. He would have qualified but which stratification he would have got is not clear. Still, I think you guys made a safe bet and I believe that a PSA of 0.01 is a success story!



tony

Jim,
The answer is not changed. OM trials do go by a different name sometimes because "ogliometastatic" is hypothesized to be 5 or less met locations in PCa. Depending on whom you talk to. The CHAARTED trial was one such trial. S1216 is another. So yes there are many OM trials out there but typically the trials are not dedicated to OM but rather they are dedicated to metastatic with OM being a subset being studied. Most of the common studies now are using Enzalutamide or Abiraterone but in the case of CHAARTED they used Taxotere.

Here's some examples:

794 trials for metastatic prostate cancer:
clinicaltrials.gov/ct2/results?term=metastatic+prostate+cancer&Search=Search

243 current trials for metastatic PCa:
clinicaltrials.gov/ct2/results?term=metastatic+prostate+cancer&recr=open

Here's an example of one that would qualify an OM patient:
clinicaltrials.gov/ct2/results?term=metastatic+prostate+cancer&recr=open

In the above trial the following would include an OM patient:
> Progression of bidimensionally measurable soft tissue (nodal) metastasis by CT scan or MRI within the past 4 weeks AND/OR

> Progression of bone disease by at least two new bone lesions on bone scan confirmed by a second bone scan

While I would not take part in that trial, I only list it to show that OM is usually not broken out in trials by the primary research but rather OM patients would be a class within a trial of metastatic patients.

So my conclusion is yes there are many trials for the OM patient, but that the term OM is not generally used.

If I were in your shoes I would have looked at all the metastatic trials at Dx (if I had todays smarts as opposed to what I actually knew at Dx). Even still there are quite a few that I could enter today even having been in remission for nearly 7 years. But I have good fortune right now and would probably stay the course. But again in your shows I would be particularly interested in trials that combine Enzalutamide with a CYP17 drug such as abiraterone or TAK700.

clinicaltrials.gov/ct2/results?term=enzalutamide+abiraterone

I would also keep a close eye on cabazatinib (XL-184) and combinations within it. All of these drugs have differing mechanisms and can all be considered together. Look for cabazatinib to reach FDA approval in 2014.

Tony

Just a follow up,
More data on the CHAARTED trial will be released at ASCO. I will be there and share. We had a great impromptu call at SWOG today on this trial and the excitement is real. On the call were some great researchers (Vogelzang, Lerner, Thompson, Hussain, etc) and the feeling is that this trial is indeed a game changer. I learned that the B arm on this trial ~ the ADT only arm ~ was a "standard of care" arm. What this means is that the ADT patients that were no longer responding to ADT were allowed to venture to other mechanisms such as chemo, Zytiga, Xtandi, etc. So the two years data is absolutely rock solid. More time is needed to see more years ahead and if the arms equalize, but for now the trial has indeed proposed a game changer for men diagnosed with extensive mets and starting their treatments for the first time. What is not clear is whether the men with lesser mets will benefit better later on. Thus more time will tell.

Peace

Tony

Thanks, Tony.

Since I am responding well to ADT at the moment, no rush.

When my friends the Wampuscats got into their clinical trial, Marie and Jim stated their goal was to actively attack the beast rather than wait for it to win round 1, I decided to start looking for clinical trials more aggressively.

Just found one on NCT00579072 - The Impact of Androgen Ablation Therapy on Cognitive Functioning and Functional Status in Men with Prostate Cancer Age 65 and Older.

Decided I better apply before I forget to do so due to the Lupron:]

LupronJim

I agree with you Jerry. Those on trials are pioneers for the rest of us. Don't know if I would ever agree to be on one, where some are giving placebo instead of real meds.

David