Celebrex

[gusgold]

Has anyone had good results lowering PSA with Celebrex and if so, what dose was used.

Gus

[pjoshea13]

Gus,

I have never used Celebrex, but I remember the studies.

Nobelist John Vane is credited with laying the groundwork for the class of selective COX-2 inhibitors. I remember reading his obituary in 2004, since Vioxx had just been withdrawn & Celebrex seemed on the ropes. About that time, a PCa study [2] was terminated early because of concerns over cardiovascular safety.

The Wiki page on Celecoxib [1] claims:

"Side effects include a 37% increase in incidence of major vascular events, which include nonfatal myocardial infarction, nonfatal stroke, or death from a blood vessel-related cause."

[2] "Celecoxib versus placebo for men with prostate cancer and a rising serum prostate-specific antigen after radical prostatectomy and/or radiation therapy."

"Patients were randomly assigned to celecoxib (400 mg by mouth twice daily) or placebo."

"Before discontinuation of the study, 78 men were assigned randomly to either celecoxib or placebo. Eight (20%) of 40 men in the placebo group and 15 (40%) of 38 men in the celecoxib group had post-treatment PSADT of more than 200% of baseline PSADT with no new metastases ... Mean PSA velocity increased by 3.0% for the placebo group and decreased by 3.4% for the celecoxib group"

[3] "A pilot study of use of the cyclooxygenase-2 inhibitor celecoxib in recurrent prostate cancer after definitive radiation therapy or radical prostatectomy."

"Twelve patients who had biochemical relapse after RT or RP were treated with celecoxib 200 mg twice daily."

"Eight of the 12 patients had significant inhibition of their serum PSA levels after 3 months of treatment; five had a decline in their absolute PSA level and three a stabilization of the level. Of the remaining four patients, three had a marked decrease in their PSA doubling time, with a mean increase (i.e. slowing) of 3.1 times that before treatment. The short-term responses at 3 months also continued at 6 and 12 months."

[4a] "Systemic therapy for advancing or metastatic prostate cancer (STAMPEDE)"

"it was felt that the potential gains from using celecoxib in the STAMPEDE population could exceed the likely risks if therapy were limited to a year and patients with previous cardiovascular disease were excluded from the trial. However, unfortunately the review of this issue and agreement to include the COX-2 inhibitor in STAMPEDE delayed the initiation of the trial by 18 months. Reassuringly, a review of the emerging safety data by the IDMC has led to the continuation of the celecoxib arms with STAMPEDE."

[4b] "Celecoxib plus hormone therapy versus hormone therapy alone for hormone-sensitive prostate cancer: first results from the STAMPEDE multiarm, multistage, randomised controlled trial"

"2043 patients were enrolled in the trial from Oct 17, 2005, to Jan 31, 2011, of whom 584 were randomly allocated to receive hormone therapy alone (control group; arm A) and 291 to receive hormone therapy plus celecoxib (arm D). At the preplanned analysis of the second intermediate activity stage, with 305 FFS events (209 in arm A, 96 in arm D), there was no evidence of an advantage for hormone therapy plus celecoxib over hormone therapy alone"

"Celecoxib 400 mg twice daily for up to 1 year is insufficiently active in patients starting hormone therapy for high-risk prostate cancer, and we do not recommend its use in this setting."

[5] "Phase II, Randomized, Placebo-Controlled Trial of Neoadjuvant Celecoxib in Men With Clinically Localized Prostate Cancer: Evaluation of Drug-Specific Biomarkers"

"Patients with localized prostate cancer and Gleason sum > or = 7, prostate-specific antigen (PSA) > or = 15 ng/mL, clinical stage T2b or greater, or any combination with greater than 45% risk of capsular penetration were randomly assigned to celecoxib 400 mg by mouth twice daily or placebo for 4 to 6 weeks before prostatectomy."

"tumor tissue had significantly lower COX-2 expression than benign prostatic tissue ... and significantly higher levels of the proliferation marker Ki-67" (!!!)

"Treatment with 4 to 6 weeks of celecoxib had no effect on intermediate biomarkers of prostate carcinogenesis, despite the achievement of measurable tissue levels. We caution against using celecoxib 400 mg twice daily as a preventive agent for prostate cancer in additional studies."

{Finding less COX-2 in PCa tissue than in benign tissue, is consistent with studies that found less arachidonic acid [AA]. COX-2 acts on AA to produce inflammatory metabolites.}

-Patrick

[1] en.wikipedia.org/wiki/Celec...

[2] jco.ascopubs.org/content/24...

[3] ncbi.nlm.nih.gov/pubmed/147...

[4a] onlinelibrary.wiley.com/doi...

[4b] ncbi.nlm.nih.gov/pmc/articl...

[5] ncbi.nlm.nih.gov/pmc/articl...

[gusgold in reply to pjoshea13]

Patrick I wonder if ....lower Cox-2 expression leads to lower ROS which = higher levels of Ki-67. At one time Myers was a big fan of Celebrex and had most of his patients on ADT also on Celebrex.

Gus