Enzalutamide Product info, FYI

[Darryl]

I got the following info regarding Enzalutamide by email...I thought to post and share, just as an FYI

MECHANISM OF ACTIONEnzalutamide is a second generation androgen receptor inhibitor

INDICATIONEnzalutamide indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer.

STUDY DESIGN & POPULATIONA global randomized double-blind, placebo-controlled Phase III trial (n=1,401) evaluating enzalutamide vs. placebo in nmCRPC patients at high risk for developing metastases (as defined by PSA doubling-time of ≤10 months and PSA above 2ng/mL):

No prior chemotherapy, immunotherapy, second generation AR antagonist, or CYP17A inhibitor

Ongoing androgen deprivation therapy (ADT) or prior orchiectomy

ECOG 0 or 1

M0 is determined by using bone scan, MRI, and/or CT

DOSING & ADMINISTRATIONEnzalutamide capsules x 4, administered once daily, without regard to food

PRIMARY ENDPOINTMetastasis-free survival (MFS): 36.6 months for enzalutamide vs. 14.7 months for placebo (increase of 22 months); HR 0.29, p < 0.0001)

OS SECONDARY ENDPOINTOverall survival (OS) data were not mature at the time of final MFS analysis but show a positive trend in OS improvement for enzalutamide vs placebo

OTHER SECONDARY EFFICACY ENDPOINTSStatistically significant improvement in time to PSA progression and time to first antineoplastic therapy.

QUALITY OF LIFENo difference between enzalutamide and placebo in the time to deterioration in health-related QOL measured by FACT-P and EQ-5D

SAFETYIncidence of All AEs (Enzalutamide vs. placebo)

Nausea: 11.3% vs 8.6%

Hypertension: 12.2 vs 5.3%

MACE: 5% vs 3%

CV Deaths: 3% vs 1%

Dizziness: 9.7% vs 4.3%

Fall: 11% vs 4.0%

Fatigue: 32.5% vs 13.7%

Mental impairment: 5.1% vs 1.9%

Additional DataIncreased incidence of seizures stated in the Prescribing Information Warning & Precautions section.

[Hidden]

Thanks for this post Darryl.

[caretkr]

Thanks for sharing. can you help me understand if metastasis free survival has an increase in 22 months means no disease progression as well right? In that case it has same benefit on overall survival or that is different?

[PhilipSZacarias]

A note to everyone on this website, I have compared the mechanism of action of enzalutamide with that of the phytochemical dindolylmethane (or DIM) which is obtained from cruciferous vegetables and found them to be (surprisingly) similar.

[BrianF505 in reply to PhilipSZacarias]

I’ve been on Xtandi for 4 1/2 years. PSA still in range of 0.04-0.07 every 4 months. Recently I added DIM to my supplement regimen. I’ll know in 4 months if that has helped reduce my PSA. In the meantime, I’d like to report a side affect of DIM. About 2 weeks into it, I noticed an increased level of calm and serenity in my life. I mentioned this to my wife and asked her if she noticed any changes. She asked when I started. I told her and she chewed on my response for a second or two and said yes, I’d become more chill. Chill is my word, not hers. Anywho- I didn’t expect this added benefit. But boy oh boy, am I happy for it.

[PhilipSZacarias in reply to BrianF505]

I am not sure if I experienced a similar "chill" effect. I attributed the more relaxed attitude to maturity (in facing my situation) and taking THC and CBD for a period of time. I have stopped taking the latter two but continue with DIM. In any case, I have not experienced any deleterious side effects and continue to feel relatively well after 2 years of ADT and with a PSA less than 0.2 ng/ml. Phil

[RJ-MN]

I have been on enzalutamide for 50 months (in conjunction with ProstVac-TriCom in a clinical trial at the NIH). PSA was 13.05 at initiation, dropped below 1.0 in 2 months and below 0.2 after 4 months. Nadir of <0.02 was reached in 13 months and held until month 20 when it was 0.03. A slow rise began exceeding 1.0 after 33 months, 2.0 after 37 months, 4.6 after 41 months, and is now at 8.18 after 50 months. Present metastases have shown increased uptakes on scans corresponding with PSA's increase, but no new mets have yet formed, which keeps me on the study.

Conundrum, of course, is whether I should stay on the study until new mets form or try to deal with the increasingly active present metastases.

[Kevinski65]

Hey dude I got in the Xtandi alone arm of the study at NIH. Going there 3 years. I'm also on Lupron.