Antineoplastics

Question 1

Goserelin, Leuprolide

Answer 1

GnRH analogs –> initially stimulate FSH and LH –> transient rise in steroid synthesis (FLARE)
- long-term continuous administration –> GnRH receptors decrease and desensitized –> decreased FSH and LH secretion
Uses - prostate cancer, premenopausal ER+ breast cancer
Tox - flare, pain, urethral obstruction, spinal cord compression
delayed - decreased testosterone

Question 2

Degarelix

Answer 2

GnRH antagonist –> competitive GnRH antagonist –> prevents LH secretion with no initial flare (much faster reduction in testosterone)
Tox - decreased testosterone, promote histamine release

Question 3

Dutasteride, Finasteride

Answer 3

5-alpha reductase inhibitors –> competitive inhibitors of 5-alpha reductase (test—->DHT)
Uses - BPH, baldness
Tox - decreased testosterone, and teratogenic

Question 4

Abiraterone Acetate

Answer 4

17alpha-hydroxylase inhibitors –> prodrug converted to competitive inhibitor of 17alpha-hydroxylase (pregnenolone –> progesterone) –> blocks ALL androgens
Uses - w/ prednisone –> metastatic castration
Tox - decreased testosterone

Question 5

Irreversible = exemestane
Reversible = aminoglutethimide, anastrozole, letrozole

Answer 5

Aromatase inhibitors –> target conversion of testosterone and androstenedione to estradiol
Uses - first line for hormone receptor
- 2nd-line tx when tamoxifen has failed
Tox - Amino = N/V, fever, adrenal insufficiency, myelosuppresion
Ana, letro, exem = nausea, headache, fatigue, polyarthralgia, decreased bone density

Question 6

Bicalutamide, Flutamide, Nilutamide

Answer 6

Anti-androgens -> inhibit ligand binding and translocation of androgen receptor to nucleus –> increased release of FSH and LH –> increased testosterone synthesis but blockade of effects
Tox - FLutamide = diarrhea, N/V, decreased testosterone, gynecomastia

Question 7

Raloxifene, Tamoxifen, Toremifene

Answer 7

compete with estrogen for binding to estrogen receptor
- antagonist in breast
- absorbed orally, peaks in 4-7 hrs, excreted in stool, no additional benefit after 5 years
Tox - increased risk of endometrial cancer, increased risk of stroke

Question 8

Fulvestrant

Answer 8

compete with estrogen for binding to estrogen receptor
- antagonist in breast
- administered intramuscularly in 1 month intervals, peaks at 7 days
Tox - GI, headache, back pain, pharyngitis