Pharm-Hormonal Management Of Cancer

Front 1

SERM: Selective Estrogen Receptro Modulators

Back 1

Raloxifene
Tamoxifen
Toremifene

Hint 1

As a class SERMS block estrogen receptors in the breast cancer cell as well as having local effects on other estrogen receptors. Only work in ER positive tumors.

Raloxifene is the equivalent to tomoxifen in post menopausal women.

Toremifene cross reacts with tamoxifen

Tamoxifen is the gold standard and works as an estrogen antagonist in breast tissue and agonist in bone and endometrium. Locally tamoxifen decreases TGF alpha a stimulatory growth factor and increases TGF beta an inhibitory growth factor. Tamoxifen ins biotransformed by CYP2D6 to endoxifen that is 100X more potent and 6X more concentrated at receptors. People who are slow metabolizers have worse outcomes. It is administeres orally and is used in treatment of metastatic breast cancer, palliation of advanced breast cancer and preventive agent for people at risk. Toxicity is acute nausea and vomiting that disappears after a few weeks. Chronic side effects are hot flashes, thrombocytopenia, leukopenia, vaginal bleeding, skin rashes, retinopathy and corneal opacities. The most important side effects are three times increased risk of endometrial cancer and thrombosis from DVT.

Front 2

AI: Aromatase Inhibitors

Back 2

Anastrozole
Letrozole
Exemestane
Aminoglutethamide

Hint 2

AIs are not used in premenopausal women b/c they stimulate the ovaries and do not suppress estrogen. This class of drugs inhibits the aromatase enzyme preventing the conversion of proproducts to estrogen.

Anastrozole and letrozole are nonsteroidal and are used in treatment of anti-estrogen resisitante breast cancer. They bind reversibly to aromatase. Toxicity causes nausea, comiting, fatigue and hot flashes

exemestane is a steroidal that irreversibly binds to aromatase.

Aminoglutethamide is a nonselective inhibitor that inhibits various enzymes thus is not used much anymore because it causes bad side effects.

other than aminoglutethamide all other AIs are interchangeable. The main toxicities of this group to worry about are arthritis and osteopenia and osteoporosis.

Compared to tamoxifen there is a lower risk of thromoembolic complications, higher risk of bone loss and fracture, and higher risk of sexual dysfunction. Also AI is ONLY for post menopausal and very important in the treatment regiment. Pre-menopausal can only be treated by SERMs

Front 3

Premenopausal patients treatments

Back 3

Early disease and late disease
-Chemotherapy +/- tomoxifen
-ovarian ablation/oophorectomy +/- tomoxifen
Tomxifen

Front 4

postmenopausal patient treatments

Back 4

Early disease
-tomoxifen or AI
-Chemo
-Chemo + tomoxifen or AI

Advanced disease
-chemo
-tomoxifen or AI
-if that fails then progestins

Front 5

LHRH agonist

Back 5

Leuprolide
Goserelin
Histrelin

Hint 5

class inhibits sex steroids in both men and women, used primarily in prostate cancer. They work at the pituitary gland as a negative feedback look to stop the body from making estrogens or androgens.

Goserelin-used for prostate cancer, breast cancer, endometriosis, endometrial thinning. Used as a depot formulation.

Histrelin is used more for precoscious puberty, is a 12 month surgical implant

Leuprolide is a sub Q monthly injection.

side effects of the class cause hot flashes, gynecomastia, tumor flare (initial increase in gonadotropin), goserelin in females (headache, vaginitis, diaphoresis), histrelin: urinary retention

Front 6

Tumor flare

Back 6

Ketoconazole
Nilutamide
bicalutamide
flutamide

Hint 6

ketoconazole-androgen synthesis inhibitor

Nilutamide, bicalutamide, flutamide-binds to androgen receptors and inhibits binding of testosterone.

Front 7

Fulvestrant

Back 7

steroid that competitively binds to estrogen receptors. The only pure estrogen receptor antagonist. FDA approved for post menopausal 2nd line drug. 250 mg IM monthly for women. Adverse effects-hot flashes, nausea, angioedema, weakness, local site reaction.

Front 8

GnRH antagonist

Back 8

Abarelix
Degralix

Hint 8

abarelix is used in advanced prostate cancer. causes severe allergic reaction thus is very restricted in those allowed to distribute it

degralix is the equivalent to leuprolide approved for treatment of advanced prostate cancer.

Front 9

Progestational Agents

Back 9

Megestrol acetate
medroxyprogesterone

Hint 9

are directly cytotoxic to breast and prostate cancer. Often used as appetitie stimulant but causes wieght gain of usually water and fat. Can cause diabetes.