150mg qd Bicalutamide and 5mg qd Proscar (casodex and finestride) for locally advanced prostate cancer

What do you think of 150mg qd Bicalutamide and 5mg qd Proscar (casodex and finestride) for locally advanced prostate cancer?

[pjoshea13]

See:

[1] "Although many prostate cancer cases relapse to a hormone-insensitive state, endocrine therapy involving androgen depletion by orchiectomy or by treatment with LHRH-analogue as well as blockade of the androgen receptor (AR) with anti-androgens remains a primary treatment option. Quality of life (QOL) however, is a prime consideration of men choosing such an approach. In this report we discuss a synergistic combination of 150-mg bicaltumide (Casodex) and 5 mg finasteride (Proscar) in the treatment of a 69-year-old patient with a relapsed (biochemical failure) Gleason score 7 prostate cancer, initially treated with external beam radiation therapy. A successful clinical outcome as evidenced by undetectable serum PSA, bone scan density and overall general well-being was accomplished with minimal side effects. Experiments using an established hormone-dependent prostate cancer cell line (LNCaP) showed that the combination of bicaltumide-finasteride at the same ratio as used clinically, produced synergistic effects on the inhibition of cell proliferation and AR expression/phosphorylation. A more complete inactivation of the AR on this regimen may have had the effect of constraining the ability of the AR to mutate, and/or diminishing the ability of androgen independent clones to evolve. Thus, passage to androgen independence may have been slowed or arrested."

[2] "Medical or surgical castration is effective in advanced prostate cancer but with profound side-effects, particularly on sexual function. Effective, less toxic therapies are needed. This study examined whether the addition of finasteride to high-dose bicalutamide enhanced disease control, as measured by additional decreases in serum prostate-specific antigen (PSA).

PATIENTS AND METHODS:

Forty-one patients with advanced prostate cancer received bicalutamide (150 mg/day). Finasteride (5 mg/day) was added at first PSA nadir. Serum PSA was measured every 2 weeks until disease progression. Questionnaires were administered to assess sexual function.

RESULTS:

Median follow-up is 3.9 years. At the first PSA nadir, median decrease in PSA from baseline was 96.5%. Thirty of 41 patients (73%) achieved a second PSA nadir and median decrease of 98.5% from baseline. Median time to each nadir was 3.7 and 5.8 weeks, respectively. Median time to treatment failure was 21.3 months. Toxicities were minor, including gynecomastia. Seventeen of 29 (59%) and 12 of 24 (50%) men had normal sex drive at baseline and at second PSA nadir, respectively. One-third of men had spontaneous erection at both time points.

CONCLUSION:

Finasteride provides additional intracellular androgen blockade when added to bicalutamide. Duration of control is comparable to castration, with preserved sexual function in some patients."

[3] "Compare the efficacy and tolerability of dutasteride in combination with bicalutamide to bicalutamide monotherapy in the treatment of locally advanced and metastatic prostate cancer (PCa).

METHODS:

One-hundred-fifty PCa patients with locally advanced or metastatic disease were prospectively enrolled and randomly assigned to receive either bicalutamide monotherapy 150 mg once daily (79 patients) or bicalutamide 150 mg plus dutasteride 0.5 mg once daily (71 patients). Treatment response was assessed by serum PSA level measurement, and standard procedures for diagnosis of clinical progression were used during follow-up. Patient-reported quality of life (QoL) was assessed using validated questionnaires (EORTC QLQ-C30 and QLQ-PR25).

RESULTS:

At 3 years follow-up, PSA progression was found in 52 patients [65.8 %; 95 % confidence interval (CI) 55.4-76.3] in the monotherapy group compared to 38 patients (53.5 %; 95 % CI 41.9-65.1) in the combined therapy group (p = 0.134). At the time of analysis 37 men (46.8 %; 95 % CI 35.8-57.8) in the monotherapy group had died versus 30 men (42.3 %; 95 % CI 30.8-53.7) in the combined therapy group. Median survival time was 5.4 and 5.8 years, respectively (p = 0.694). There was no statistically significant difference in the presentation frequency of adverse events between groups (p = 0.683). QoL was good and comparable between the two groups.

CONCLUSIONS:

Both therapies were well tolerated with a good QoL. However, despite a trend toward higher efficacy of the combined therapy, progression-free survival and overall survival was not significantly different between the groups. Further research on this therapy should be performed."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/151...

[2] ncbi.nlm.nih.gov/pubmed/151...

[3] ncbi.nlm.nih.gov/pubmed/273...

[Hidden in reply to pjoshea13]

Awesome! Thanks. Looks like dutasteride is better at blocking DHT than finasteride.

[BILIE in reply to pjoshea13]

I, a 'lurker', age 78, have been using Casodex (25mg/d - (I weigh only 105#)) intermittently (roughly 3 mos on - 2mos off) with Proscar(5mg/d) NOT intermittently, but daily. I go back on the Casodex at PSA 5-6; and stop Casodex at PSA 1.0 or a bit less. This has worked for me for aprox 45 mos now.

My hx is: Surgical removal of prostate 26 yrs ago at age 52; Biopsy (evaluated twice) = Gleason: (5 + 2) with sem ves invasion; biochemical failure aprox 6 yrs post surgery; avid exerciser; eat healthily; weight ideal. Side effects of Casodex = decreased erection ability and moderate breast formation / Side effects of Proscar = increased incontinence and decreased erection ability.

Over these many years I have GREATLY APPRECIATED Patrick's intelligently researched and generously provided inputs - imo he is a TREASURE to be valued highly - THANKS AGAIN PATRICK !!

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

Nice to see that you've come out of the shadows... Ditto on Patrick's kudos....

Good Luck, Good Health and Good Humor.

J-o-h-n Friday 08/30/2019 4:01 PM DST - Pinnes

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

THANKS J-O-H-N !!

[Tall_Allen]

It’s not as powerful as a GnRH agonist but if you find the side effects more tolerable, it’s not unreasonable.

[Hidden in reply to Tall_Allen]

The side effects of GnRH agonists are what I'm trying to get away from.

[Break60 in reply to Hidden]

Well think about estradiol patches instead of bicalutamide or oriscar or dutasteride .

See ncbi.nlm.nih.gov/pmc/articl...

[Hidden in reply to Break60]

I was on estrogen patches for 5 months. Zero depression. Test undetectable. But gnyo, loss of strength, and the big problem: no libido. I lost about 8 lbs of fat and 12 lbs of muscle while on estrogen.

PSA is undetectable (<0.02) and has been undetectable since RP in December 2018.

[Break60 in reply to Hidden]

If you go on a Lupron like drug you’ll gain weight ,lose muscle, have joint pain, lose stamina and have no libido , be fatigued , have weaker bones and have hot flashes. A lot worse than estradiol by far! Plus you can stop the patches any time but Lupron is an injection which you can’t reverse.

[MateoBeach]

Yes, the research is provided here. Agree with T_A that it is an alternative to LHRHa with less side effects for some (including me) and more uncertainty about durability of efficacy.

My personal experience: I could not tolerate LHRH so I opted for bicalutamide 50 mg and dutasteride 1 mg (2 X 0.5) per day. My fast rising PSA (PSADT 3 mo) was at 5 and went down to 0.02 lasting for 4.5 years. Then it began rising again at the 3 month PSADT. Side effects and QOL were much better for me, and felt more "like myself" because testosterone is still present. Apparently sometimes bicalutamide can at some point permit or even promote PC tumor growth. So I stopped the regimen 6 months ago, PSA actually dropped some (0.25 to 0.21) and now is rising very slowly as I consider my next treatment plan. (Radiation to lymph nodes shown on Ga-PSMA scan and pelvic radiation plus Lu-PSMA treatment in Australia.)

I think my own next ADT regimen, when needed, will be centered on topical estradiol (patch or gel). I am not aware of any good trial(s) that shows it is inferior to LHRH.

[Hidden in reply to MateoBeach]

I'm sort of thinking along the same lines. I might try the BD (bicalutamide/dutasteride) for 3-6 months and then switch back to estrogen patches for a few months.

[Break60 in reply to Hidden]

I take dutasteride, metformin, rosuvastatin, celecoxib and duloxetine along with the patches.

[Hidden in reply to Break60]

I started dutasteride today. I've been taking metformin for a few years now. I'm taking rosuvastatin but might switch to one with a shorter half-life. I was thinking simvastatin. Lipophilic.

[Break60 in reply to Hidden]

Snuffy prefers rosuvastatin

[Hidden in reply to Break60]

Snuffy and COC prefer rosuvastatin. I can't sleep at night ever since starting it. Could be something else but a known side effect of statins is insomnia. Only happens in 5-10% of people but I might be one of those people.

I stopped it for now and if in a day or so my sleep issues go away I'm going to try a shorter half life statin (rosuva has a 14 hour half life but some of it's metabolites are around 35 hours, sim has a 3 hour half life).

[Hidden in reply to Hidden]

Continued trying Rosuvastatin. Every other day. Cut dose in half, then halved again. Took in the morning. Early. Late. Terrible insomnia. I started simvastatin. If I take it before bed (cholesterol is mostly produced at night), I have bad insomnia. But if I take it in the morning, while perhaps not as effective, I can sleep. Also taking red yeast rice (one of the constituents is the same as the active drug in lovastatin). No problem with insomnia and I can even take it at night.

[Break60 in reply to MateoBeach]

I’m sure there won’t be any more trials since estradiol is natural and pharmaceutical companies can’t make money and in fact will lose a lot of money if lhrh agonists see reduced sales which they certainly should !

[Hidden in reply to Break60]

True. The companies aren't nonprofits so maximize revenue. That can sometimes suck for us though.

[MateoBeach]

Oh yes, additionally I received three radiation treatments to my breast tissues prior to starting this regimen. (I had a small degree of gynecomastia at that time that justified medicare coverage of the treatments). The regimen did increase the breasts somewhat, but only to a moderate and stable amount, not enough to appear feminized.

[AlmostnoHope]

Works great intermittently. Even better if you add PCSPES to it. I wouldn't have made it this far without it.