Name

Prescription Meds of Interest to PCa Patients – v. 5/4/13 This document is most conveniently viewed on a computer because it contains internal bookmarks/links (e.g., from the meds in the index on pages 1-3 to the more detailed summary on the pages that follow) and some hyperlinks to external web pages. A list of document abbreviations & conventions is shown on the last page.
Meds Index
Medication
Category
Second line ADT – to suppress testosterone Lowers estrogen (for unusual circumstances) Low risk agent; may reduce androgen receptor sensitivity Molecularly targeted therapy (tyrosine-kinase inhibitor) Misc (moderate risk) agent to slow PCa growth rate Molecularly targeted therapy (tyrosine-kinase inhibitor) Statin to lower cardiovascular risk; possible anti-tumor effect Reduces ADT bone loss & skeletal-related events (MAB) Higher risk agent to slow PCa growth rate (esp. for CRPC) Low risk agent; may reduce androgen receptor sensitivity Second line ADT – binds to androgen receptor To mitigate bone loss & hot flashes from ADT Prescription Meds of Interest to PCa Patients – v. 5/4/13 Lowers estrogen (for unusual circumstances) Statin to lower cardiovascular risk; possible anti-tumor effect Misc (low risk) agent to slow PCa growth rate Second line ADT – to suppress testosterone Statin to lower cardiovascular risk; possible anti-tumor effect Molecularly targeted therapy (tyrosine-kinase inhibitor) Prescription Meds of Interest to PCa Patients – v. 5/4/13 To lower cardiovascular risk; possible anti-tumor effect Second line ADT – to suppress testosterone To mitigate bone loss & hot flashes from ADT Reduces ADT bone loss & skeletal-related events (MAB) Second line ADT – binds to androgen receptor Statin to lower cardiovascular risk; possible anti-tumor effect Reduces ADT bone loss & skeletal-related events Second line ADT – to suppress testosterone Prescription Meds of Interest to PCa Patients – v. 5/4/13 Application
How Administered
Benefits
Mechanism of Action
Side Effects/Cautions
(leuprolide)
advanced PCa. The most from 1-4 months. Some castrate level (monitoring production of testosterone (via a include osteoporosis, metabolic from Abbott Labs deprivtion) drug initially combining with ongoing effectiveness). This lowers Casodex, Avodart & low- tumor load, which can make Firmagon
Monthly injections to the No initial testosterone surge; (degarelix)
Lupron). A 2010 study found production (in 1-3 days) Approved 1995 for use in Oral- Myers uses from (bicalutamide)
flare when given a week prior (blocks action of androgens). It Occasional stomach upset and liver subsequently launched as aggressiveness and PSA oncologists believe ongoing use of Casodex with Lupron is receptors, and also by Nilandron
(nilutamide)
from Sanofi-Aventis line hormonal therapy Approved 2002 for BPH. Oral-1X/day. Monitor (dutasteride)
of ADT3 therapy, or used reduce dose as indicated evidence that DHT is a key Myers’ active surveillance DHT target is < 5 ng/dL.
Prescription Meds of Interest to PCa Patients – v. 5/4/13 Application
How Administered
Benefits
Mechanism of Action
Side Effects/Cautions
See above. Use of Avodart or Longer track record than (finasteride)
Proscar will lower DHT level. Avodart; essentially same Reduces bone loss from ADT; A bisphosphonate. Attaches to (zoledronic acid) treating osteoporosis &
Reduces bone loss from ADT; Inhibits RANK ligand, a protein Potential complication is (denosumab)
metastases. Works better than (bone resorption) Oral-3X/day (titrate dose Anti-tumor activity (35-50% (ketoconazole)
antifungal drug; first used initially). Combining response rate, which is similar through two mechanisms: (1) with Leukine & estrogen to Taxotere). This is in (sargramostim)
chemotherapy and extend the (Granulocyte Macrophage- Colony Stimulating Factor) that heartburn. WBC should be closely chemotherapy. Frequently multiple other agents used with PCa to stimulate including ketoconazole & Prescription Meds of Interest to PCa Patients – v. 5/4/13 Application
How Administered
Benefits
Mechanism of Action
Side Effects/Cautions
Taxotere
Approved 2004 for CRPC. One hour infusion every Anti-tumor activity (40-50% (docetaxel)
reproduction; induces cancer cell among chemotherapy drugs. Side used chemotherapy agent weekly treatment has also median survival advantage, from Sanofi-Aventis for PCa. Appropriate disrupting microtubular network including fatigue, nausea, tingling Oral—1X/day. Essential Most intense & complete form Zytiga inhibits CYP17 via a (abiraterone
CRPC post-Taxotere. Not to take on empty mechanism that is 20 times more interaction and liver saturation acetate)
rather another second-line combined with Lupron Importantly, Zytiga acts against changes in serum potassium levels undetectable in some patients). androgens produced within the production of testosterone sometimes Inspra).
Provenge
Treatment series consists 2002 Provenge trial found (sipuleucel-T)
metastatic CRPC. The first of 3 doses at 2-week immune cell “sensitizing” 2005 trial found men w/ expressed in 95% of all PCs. The analysis has stirred up controversy likely to be alive at 36 months. via activated T cells that kill the Median survival advantage on PCa cells.
Provenge = 4.1 months.
Anti-tumor activity; prolongs Mechanism of action is very (cabazitaxel)
life after Taxotere fails. What similar to Taxotere’s. Possibly a Taxotere, except for bone marrow better initial chemotherapy drug suppression.
from Sanofi-Aventis post-Provenge. Another Approved March 2011 as 90-minute infusions Yervoy blocks protein CTLA-4, Some patients experience major (ipilimumab)
every 3 weeks for a total Yervoy, in addition to being which inhibits the synthesis of T immune-related adverse reactions, effective for advanced disease, cells (an immune system from Bristol-Myers melanoma; currently in could have significant benefit component). This results in Prescription Meds of Interest to PCa Patients – v. 5/4/13 Application
How Administered
Benefits
Mechanism of Action
Side Effects/Cautions
(enzalutamide/
CRPC post-Taxotere. This already talk about trying Feb 2010 showed nearly 5- the androgen receptor compared based on Phase III trial, although MDV3100)
combination with Zytiga advantage for Xtandi vs. alternative to Zytiga, with testosterone production; a different mechanism. A Xtandi to prevent the Alpharadin
Monthly injections for 4- Trials showed 2.8 month (radium-223
chloride)
Cometriq
(cabozantinib/
trials underway for CRPC intermittent dosing VEGF pathways. MET is highly was fatigue (16%); numerous other II patients to need dose reduction).
metastases. FDA approved Nov 2012 for medullary thyroid cancer.
Orteronel
(TAK-700)
androgen production. May be biosynthesis pathway. effective at doses that won’t require use of prednisone.
Galeterone
(TOK-001)
mechanism of action. Phase I binding to the androgen receptor trial results were encouraging (as does MDV 3100) (3) decreases overall androgen receptor levels in prostate tumors Prescription Meds of Interest to PCa Patients – v. 5/4/13 Application
How Administered
Benefits
Mechanism of Action
Side Effects/Cautions
PROSTVAC
Monthly injections of an Phase II trial showed a Poxviruses used to sensitize the Very good initial safety and median survival advantage on immune system to PSA, then PROSTVAC of an impressive boost immune response via & LFA-3. This enables a vigorous T cell response.
Tasquinimod
metastatic activities. Known to loss, fatigue, pain, and stomach density but exact mechanism is not known.
Custirsen
Weekly infusions (taken Phase II trials showed a 40- (OGX-011)
60% improvement in survival themselves from chemotherapy mild and those frequently linked when Custirsen was added to by over-producing an enzyme Taxotere—compared to using called clusterin. Custirsen Approved in 2006 to treat Oral—1X/day (either as Sprycel has relatively low Targets oncogene Src and other Somewhat tricky drug to use, (dasatinib)
Approved 1984 to reduce Oral—2X or 3X/day; (pentoxifylline)
symptoms of claudication vitamin E supplement (pain/cramping/fatigue in sometimes used to arm & leg muscles caused enhance Trental’s activation (blood flows better in small arteries) Depakote
(valproic acid)
anticonvulsant; also used usually in combination understood. Inhibits the enzyme normal Depakote dosing levels for to control manic episodes. with other agents such as pathways disrupted by PCa in histone acetylation, resulting in PCa.
Prescription Meds of Interest to PCa Patients – v. 5/4/13 Application
How Administered
Benefits
Mechanism of Action
Side Effects/Cautions
Thalomid
In one PCa trial, time to PSA Thalidomide inhibits release of Requires strict controls to prevent (thalidomide)
progression was significantly tumor necrosis factor-alpha, increases the number of T cells tolerated, although drowsiness showed PSA declines and striking reductions in measurable disease on scans.
Revlimid
However, a phase III trial was Multiple mechanisms of action Same caution as thalidomide for (lenalidomide)
after Revlimid combined with thalidomide. Most trial data Revlimid or thalidomide for good initial results in one placebo. Other trials of Oral or via infusion. Info Reduces PSA; can extend the While immunosuppressive at (cyclophosphamide) immunosuppressive cancer on dosing and other
“holiday time” when used in higher doses, Cytoxan is showed promising response for Taxotere-resistant PCa.
Dostinex
(cabergoline)
prostate cells less sensitive to from the pituitary gland. It is Prescription Meds of Interest to PCa Patients – v. 5/4/13 Application
How Administered
Benefits
Mechanism of Action
Side Effects/Cautions
Statins, e.g.,
Reduces risk of heart disease Statins inhibit the enzyme Pravachol
and stroke. May also have a HMG-CoA reductase, which (pravastatin)
lowering LDL cholesterol. night for statins with These meds are appropriate short half-lives) synthesizing cholesterol in the weakness. This side effect can be (atorvastatin)
(simastatin)
(rosuvastatin)
Celebrex
Oral—200 mg 2X/day is Evidence of substantial Celebrex’s antitumor activity Should be avoided by patients (celecoxib)
appears to be primarily due to with a history of ulcers/GI phase II trial, extending PSA something other than COX-2 Appropriate to consider for among others, used 400 doubling time, at least in the inhibition. Someve cardiovascular risk (clotting, ↑BP, PCa patients following metformin
Oral—500 mg 3X/day in Recent phase II preliminary Metformin activates AMPK, latest study (standard for esults indicated approved in 1994 for type 2 diabetes). Other studies metformin (monotherapy) when combined with chemo mTOR pathway.
agents. Three studies show positive Provides a hormone, a type of Most common side effect is (megestrol acetate)
synthetic progesterone, to help appetite stimulation/weight gain; medroxyprogesterone To mitigate hot flashes
Injections—200-400 mg Similar results & concerns acetate (MPA)
from ADT. FDA approved (6-12 month intervals) Prescription Meds of Interest to PCa Patients – v. 5/4/13 Application
How Administered
Benefits
Mechanism of Action
Side Effects/Cautions
Vivelle-Dot
Transdermal skin patch- At low dose, can mitigate (estradiol patch)
patch form of estrogen is ADT, including osteoporosis testosterone by an enzyme & hot flashes. At high dose, called aromatase. (An estrogen (DES) because can be an effective ADT, of lower cardiovascular used as a substitute for testosterone to fall, estradiol similarly falls.
Oral—12.5-37.5 mg/day Some studies suggest (venlafaxine)
depresssion is also an issue, role in regulating the “thermo-this may be the first-choice Neurontin
Oral—300-900 mg total, A good option to try for (gabapentin)
Proposed mechanisms include & fatigue. Tolerance increases modification of adrenergic & over time. Avoid abrupt Arimidex
Reduces cardiac risk, weight These drugs are aromatase (anastrozole)
med. 1X/day was found gain, & gynecomastia some- inhibitors. They bind to the aromatase enzyme responsible taking these meds. Femara Ideal range in men is 22-30 testosterone to estradiol. (letrozole)
mortality rates, but causality has not been established.
Prescription Meds of Interest to PCa Patients – v. 5/4/13 Document Abbreviations:
5AR – 5 Alpha Reductase (an enzyme that converts testosterone to the more potent dihydrotestosterone)ADT – Androgen Deprivation Therapy (sometimes called hormone therapy, hormone blockade, androgen suppression therapy, or testosterone inactivating pharmaceuticals)CRPC – Castration-Resistant Prostate Cancer (sometimes called hormone-refractory prostate cancer or androgen-independent prostate cancer)DHT – DihydrotestosteroneDNA – Deoxyribonucleic Acid (contains genes and other important cellular instructions/information) ED – Erectile DysfunctionGI – GastrointestinalGM-CSF – Granulocyte-macrophage colony-stimulating factor, a white blood cell growth factor LDL – Low-Density Lipoprotein (the “bad” form of cholesterol)LHRH – Luteinizing Hormone-Releasing Hormone (A hormone released from the brain in response to dropping levels of testosterone. This signals the pituitary gland to release a hormone [LH] that instructs the testicles to begin production of testosterone.)MAB – monoclonal antibodyMed – medicationMets – metastasesPCa – Prostate CancerPSA – Prostate-Specific AntigenRT – Radiation TherapyWBC – White Blood Cells Document Conventions:
– exploratory drugs available via trials or in some cases expanded access programs, but not yet FDA-approved for any purpose Drugs names that begin with a capital letter are either brand names or research designations (e.g., MDV3100) Drug names that begin with a lower-case letter are generics or the non-proprietary drug name prior to a generic being available

Source: http://www.mymethow.info/docs/MOI.pdf