Enzalutamide & Abiraterone ... higher T = more favorable prognosis.

[pjoshea13]

New Japanese study, below [1].

"The role of the target serum testosterone (TST) level in enzalutamide- (Enza) and abiraterone (Abi)-treated castration-resistant prostate cancer (CRPC) patients was studied. In total, 107 patients treated with Enza and/or Abi at Chiba University Hospital and affiliated hospitals were studied."

"In the Abi and Enza groups overall, TST ≥ 13 ng/dL (median) (Hazard Ratio (HR) 0.43, ...) remained an independent prognostic factor for PFS {progression-free survival}."

"TST showed significant correlation with PFS periods"

"a longer PFS at first-line therapy showed a favorable prognosis in the Enza group"

"The TST level and PFS of first-line therapy may be considered when determining the treatment strategy for CRPC patients."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/309...

J Clin Med. 2019 Apr 11;8(4). pii: E489. doi: 10.3390/jcm8040489.

Higher Serum Testosterone Levels Associated with Favorable Prognosis in Enzalutamide- and Abiraterone-Treated Castration-Resistant Prostate Cancer.

Sakamoto S1, Maimaiti M2, Xu M3, Kamada S4, Yamada Y5, Kitoh H6, Matsumoto H7, Takeuchi N8, Higuchi K9, Uchida HA10, Komiya A11, Nagata M12, Nakatsu H13, Matsuyama H14, Akakura K15, Ichikawa T16.

Author information

1

Department of Urology, Chiba University Hospital, Chiba 260-8670, Japan. [e-mail].

2

Department of Urology, Chiba University Hospital, Chiba 260-8670, Japan. [e-mail].

3

Department of Urology, Chiba University Hospital, Chiba 260-8670, Japan. [e-mail].

4

Department of Urology, Yokohama Rosai Hospital, Yokohama 222-0036, Japan. [e-mail].

5

Department of Urology, Asahi Central Hospital, Aashi 289-2511, Japan. [e-mail].

6

Department of Urology, Japan Community Healthcare Organization Tokyo Shinjuku Medical Center, Shinjyuku 162-8543, Japan. [e-mail].

7

Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube 755-0046, Japan. [e-mail].

8

Department of Urology, Chiba University Hospital, Chiba 260-8670, Japan. [e-mail].

9

Department of Urology, Funabashi Medical Center, Funabashi 273-8588, Japan. [e-mail].

10

Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-0914, Japan. [e-mail].

11

Department of Urology, Chiba University Hospital, Chiba 260-8670, Japan. [e-mail].

12

Department of Urology, Yokohama Rosai Hospital, Yokohama 222-0036, Japan. [e-mail].

13

Department of Urology, Asahi Central Hospital, Aashi 289-2511, Japan. [e-mail].

14

Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube 755-0046, Japan. [e-mail].

15

Department of Urology, Japan Community Healthcare Organization Tokyo Shinjuku Medical Center, Shinjyuku 162-8543, Japan. [e-mail].

16

Department of Urology, Chiba University Hospital, Chiba 260-8670, Japan. [e-mail].

Abstract

Testosterone plays a significant role in maintaining the tumor microenvironment. The role of the target serum testosterone (TST) level in enzalutamide- (Enza) and abiraterone (Abi)-treated castration-resistant prostate cancer (CRPC) patients was studied. In total, 107 patients treated with Enza and/or Abi at Chiba University Hospital and affiliated hospitals were studied. The relationships between progression-free survival (PFS), overall survival (OS), and clinical factors were studied by Cox proportional hazard and Kaplan-Meier models. In the Abi and Enza groups overall, TST ≥ 13 ng/dL (median) (Hazard Ratio (HR) 0.43, p = 0.0032) remained an independent prognostic factor for PFS. In the Enza group, TST ≥ 13 ng/dL (median) was found to be a significant prognostic factor (HR 0.28, p = 0.0044), while, in the Abi group, TST ≥ 12 ng/dL (median) was not significant (HR 0.40, p = 0.0891). TST showed significant correlation with PFS periods (r = 0. 32, p = 0.0067), whereas, for OS, TST ≥ 13 ng/dL (median) showed no significant difference in the Abi and Enza groups overall. According to Kaplan-Meier analysis, a longer PFS at first-line therapy showed a favorable prognosis in the Enza group (p = 0.0429), while no difference was observed in the Abi group (p = 0.6051). The TST level and PFS of first-line therapy may be considered when determining the treatment strategy for CRPC patients.

KEYWORDS:

abiraterone; androgen deprivation therapy; castration resistant prostate cancer; enzalutamide; prostate cancer; testosterone

PMID: 30978937 DOI: 10.3390/jcm8040489

[George71]

Hi Patrick,

I was wanting your opinion on DIM.

I am reading where DIM actually blocks T and DHT when taken in excess of 100 mg dose daily. If true then it is similar to Casodex and would not be desirable for me trying to keep my T levels up and not go onto Casodex or ADT. I did start taking 9mg Boron daily for 2 days and my PSA dropped from .6 to .5 -- other only other thing I am doing other than supplements (curcumin etc) is Avadart which knocks out the DHT only. My T was 567 -- I'm afraid the DIM will block T to the PCa and have an ADT effect--- what are you thoughts please

[pjoshea13 in reply to George71]

Hi George,

I have used DIM at 400 mg & higher for many years.

I wasn't aware of it being an antiandrogen, but just found this old paper:

ncbi.nlm.nih.gov/pubmed/126...

Perhaps Nalakrats will comment. He has been in contact with Zeligs (BR-DIM creator) in the past & could pose your question to him.

If you try BR-DIM & check your PSA, that might answer your question.

-Patrick

[George71 in reply to pjoshea13]

"To examine the androgen antagonist effects of DIM, we conducted a series of cell proliferation and gene activation studies in androgen-dependent (LNCaP) and androgen-independent (PC-3) human prostate cancer cell lines. LNCaP cells were derived from lymph node metastasis, and PC-3 cells were derived from bone metastasis (22, 23, 24, 25). We found that DIM is a strong antiandrogen that inhibited androgen-dependent tumor cell growth and competitively inhibited androgen receptor translocation and signal transduction. In addition, DIM down-regulated prostate-specific antigen (PSA) expression at the transcriptional level. Results from androgen receptor (AR) competitive binding assays, nuclear translocation studies, and structural modeling computations suggest that DIM disrupts AR function in a manner similar to a chemically dissimilar synthetic antiandrogen, Casodex. Our results identify DIM as a structurally novel, naturally occurring, pure androgen antagonist of potential cancer preventive and therapeutic usefulness for prostate cancer. "

jbc.org/content/278/23/2113...

My concern is, when someone is trying to maintain high Testosterone (T) levels

( which I am) under the concept that T is therapeutic -- and since cutting off of T leads to CRPCa .... then DIM, like Casodex, --- cuts off the T to the cancer cells leading to CRPCa and defeats any benefit of maintaining high T levels. Having high blood T levels would be cancelled by the Casodex effect of DIM at high levels above 100 mg daily.

Yes / No ?

[pjoshea13 in reply to George71]

I doubt that DIM will have much of an effect. Like I said - try it (for a month, say) & not any PSA change.

-P

[j-o-h-n in reply to pjoshea13]

Try DIM SUM? Of course, surely one of my favorite Chinese snacks.

Good Luck, Good Health and Good Humor.

j-o-h-n Sunday 04/14/2019 6:13 PM DST