ADT not enough. What is the best order of treatment?

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ADT not enough. What is the best order of treatment?

Jim Marshall (not a doctor) said ...

This study is about:

• men with prostate cancer that has spread, and 
• whose hormone therapy (ADT) is no longer enough to stop their PSA rising.

More technically these men are said to have metastatic castration-resistant prostate cancer (mCRPC for short).
After their PSA began rising after hormone therapy men in this study had two or three of the following treatments:

• DOC: Docetaxel (Taxotere)
• CABA: Cabazitaxel (Jevtana)
• ART: Either enzalutamide (Xtandi) OR abiraterone (Zytiga) but not both.

This study compared different orders of giving the treatments.
It turned out that the sequence:
        ADT ➜ DOC ➜ CABA ➜ ART
had the best survival.
(That is, men who had Docetaxel, then Cabazitaxel, then one of Enzalutamide or Abiraterone lasted longest on average.)
But

• The best clinical trials recruit patients specifically for the trial (prospective) and then follow them.
• This trial was not prospective. The figures were gathered from records of men who had already been treated (retrospective). Your doctor will not regard this evidence as strong as a prospective trial.
• Your doctor will probably not yet have taken this research into account. It was published in August 2018.
• The survivals given are median (a type of average). Half the men lived longer than the median, some much longer.

... end Jim

Clin Genitourin Cancer. 2018 Aug;16(4):e777-e784. doi: 10.1016/j.clgc.2018.02.016. Epub 2018 Feb 23.

Results of the FLAC European Database of Metastatic Castration-Resistant Prostate Cancer Patients Treated With Docetaxel, Cabazitaxel, and Androgen Receptor-Targeted Agents.

Angelergues A¹, Efstathiou E², Gyftaki R², Wysocki PJ³, Lainez N⁴, Gonzalez I⁵, Castellano DE⁶, Ozguroglu M⁷, Carbonero IG⁸, Flechon A⁹, Borrega P¹⁰, Guillot A¹¹, Balea BC¹², Le Moulec S¹³, Esteban E¹⁴, Munarriz J¹⁵, Rubio G¹⁶, Birtle AJ¹⁷, Delanoy N¹, Bellmunt J¹⁸, Oudard S¹⁹.

Author information

 

 In Library !

 

Abstract

BACKGROUND:

Several agents have demonstrated an overall survival (OS) benefit in patients with metastatic castration-resistant prostate cancer (mCRPC); however, the optimal sequencing of these therapies is unknown as a result of a lack of prospective randomized controlled trials. This retrospective study aimed to identify clinical factors influencing outcomes and to determine optimal treatment sequencing in patients with mCRPC treated with cabazitaxel (CABA) and/or androgen receptor-targeted agents (ART) after androgen-deprivation therapy (ADT) and docetaxel (DOC).

PATIENTS AND METHODS:

Records of 574 consecutive patients treated (2012-2016) at 44 centers in 6 countries were retrospectively examined.

RESULTS:

A total of 267 patients received ADT → DOC → CABA (group 1), 183 patients ADT → DOC → ART → CABA (group 2), and 124 patients ADT → DOC → CABA → ART (group 3), with respective median OS from diagnosis of mCRPC of 38.3, 44.45, and 53.9 months (P = .012 for group 3 vs. group 1). Multivariate analysis showed response to first ADT ≤ 12 months, Gleason score of 8 to 10, clinical progression, and high prostate-specific antigen levels at mCRPC diagnosis were associated with worse OS. Prior receipt of ART did not influence activity of CABA.

CONCLUSION:

OS appeared to increase with the number of life-extending therapies, with a sequence including DOC, CABA, and an ART providing the greatest OS benefit.

Copyright © 2018 Elsevier Inc. All rights reserved. [Highlighting and colouring (except the title) by Jim and not the author.]

KEYWORDS:

ART; Metastatic CRPC; Survival; Taxanes; Treatment sequence

PMID:

 

29550200

 

DOI:

 

10.1016/j.clgc.2018.02.016

[Charles (Chuck) Maack]

What gives me concern is that this study looked at men treated “prior” to the approval and availability of abiraterone and enzalutamide pre-chemotherapy with docetaxel/Taxotere; thus, ADT to docetaxel was the prerequisite prior to availability of either abiraterone or enzalutamide. 

 

More recently, with the approval of these two medications “prior” to having to move to chemotherapy, I would be more interested in the overall survival (OS) or length of time prior to PSA elevation following prescribing of either abiraterone or enzalutamide – or the one after the other if one or the other showed failure – prior to having to move to the more toxic docetaxel or cabazitaxel.

 

But with the foregoing being said, in my research men with high grade prostate cancer at diagnosis are recommended to ADT and “immediate” docetaxel followed after completion of docetaxel series by enzalutamide added to the continuing ADT; not necessarily directly to cabazitaxel.

 

I have involved myself in deep research and study regarding androgen deprivation therapy (ADT) since this became “my life,” and earlier treatment for men with high grade and likely already metastasized prostate cancer at diagnosis. My personal results are explained in the following paper.  Please note that I try to look at when to begin ADT and when to move to docetaxel.  Note, too, that a couple of the reference url’s no longer open indicating the originating source has removed their article – likely either because newer info has become available or they set a time limit before removing their articles from their website.

 

The very thought that we must move beyond either surgical removal of the prostate or radiation to the prostate and its periphery is disconcerting.  Thus, we patients have to educate ourselves so that when any further treatment is necessary, we have a pretty good idea from what we have learned would be most appropriate for each of us depending on diagnostics.  My research and understanding have served me well for 22 years post my recurrence and still not having to move to chemotherapy with the toxic drugs docetaxel/Taxotere or cabazitaxel.

 

http://www.theprostateadvocate.com/pdf/Triple Hormonal Blockade ADT3.pdf