New study below [1].
There is sometimes confusion as to the reason for ADT continuation when it has "failed" [CRPC]. Androgen deprivation itself does not fail, but the cancer has found a work-around with the androgen axis generally continuing to be the major player, so it makes sense to continue ADT.
Some have asked whether ADT is really required with Zytiga (abiraterone). After all:
"Abiraterone acetate (AA) is a potent and selective inhibitor of CYP17, which is required for androgen biosynthesis in the testes, adrenal glands, and prostate tissue." [2]
"Crucially, experimental evidence suggests that the testosterone suppression achieved by abiraterone monotherapy is not sustained in non-castrated men and is overcome by a subsequent twofold–threefold surge in luteinising hormone (LH) levels [level of evidence (LoE): 2b]. Conversely, the addition of abiraterone to backbone ADT results in sustained decreases in testosterone and adrenal steroid concentrations . Although the pharmacokinetic study of O’Donnell et al. assessed a small number of men, it does suggest a need to maintain castrate levels of testosterone with ADT when initiating abiraterone therapy." [3]
...
But what about ADT with Enzalutamide? "... there is a paucity of evidence on continuing androgen-deprivation therapy (ADT) for mCRPC."
"concomitant ADT showed a significant association with longer overall survival"
-Patrick
[1] ncbi.nlm.nih.gov/pubmed/302...
Prostate Cancer Prostatic Dis. 2018 Sep 13. doi: 10.1038/s41391-018-0088-z. [Epub ahead of print]
Importance of androgen-deprivation therapy during enzalutamide treatment in men with metastatic castration-resistant prostate cancer following chemotherapy: results from retrospective, multicenter data.
Jeong CW1, Kang M2, Il Jung S3, Kim TH4, Park SW5, Joung JY6, Jeon SS2, Hong JH7, Lee JY8, Chung BH9, Ahn H7, Kim CS7, Kwon DD3, Kwak C10.
Author information
Abstract
BACKGROUND:
Enzalutamide can significantly prolong the survival of patients with metastatic castration-resistant prostate cancer (mCRPC). However, there is a paucity of evidence on continuing androgen-deprivation therapy (ADT) for mCRPC. Here, we analyzed the effect of concomitant ADT during enzalutamide treatment in men with mCRPC following chemotherapy.
METHODS:
We retrospectively reviewed the medical records of 232 patients with mCRPC who received oral enzalutamide (160 mg per day) following chemotherapy at 9 tertiary centers in Korea between 2014 and 2016. The primary endpoint was overall survival, while secondary endpoints included time to prostate-specific antigen (PSA) progression and radiographic progression-free survival.
RESULTS:
The median age of the patients was 71 years (interquartile range, 64-75 years). The proportion of patients in a grade group ≥4 was 77.6%. The rate of concomitant ADT was 29.3%, and the all-cause mortality rate was 27.1% (n = 63). Median overall survival, time to PSA progression, and radiographic progression-free survival were 24.0, 8.0, and 10.0 months, respectively. Notably, concomitant ADT showed a significant association with longer overall survival (median duration not reached vs. 18.2 months; p = 0.008). After adjusting for confounding factors, concomitant ADT was still associated with longer overall survival (hazard ratio, 0.35; 95% confidence interval, 0.17-0.72).
CONCLUSION:
Concomitant ADT during enzalutamide treatment may improve the survival of patients with mCRPC following chemotherapy.
PMID: 30214035 DOI: 10.1038/s41391-018-0088-z
RT with ADT Relogolix (Orgovyx) vs Enzalutamide (Xtandi) Side Effect Differences?
Enzalutamide (Xtandi) or not
Xtandi (enzalutamide) from India
Zytiga or Xtandi effective again after chemo?
