B-36. Cancer chemotherapy IV (Hormonal agents)

Question 1

Hormonal therapy groups

Answer 1

• Progesterone derivatives
• Anti-estrogens
• Aromatase inhibitors
• GnRH analogs
• Anti-androgens
• Corticosteroids

Question 2

Progesterone Derivatives drugs

Answer 2

1. Medroxyprogesterone acetate
2. Megestrol

Question 3

• Medroxyprogesterone acetate and megestrol
  
  • MOA?
  • Indications?

Answer 3

• Medroxyprogesterone acetate and megestrol
  
  • MOA: ↓ LH / FSH secretion → ↓ estrogen secretion from ovary → ↓ DNA/RNA synth in estrogen-dependent cells
  • Indications: endometrial carcinoma and metastatic breast cc.

Question 4

• Tamoxifen and Toremifene
  
  • MOA
  • Indications
  • Side effects

Answer 4

Tamoxifen and Toremifene

• MOA: selective estrogen receptor modulators (SERMS) → atg breast ERs but agonist on bone ER
• Indications: ER+ breast cancers (via oral admin daily for years)
• Side Effects:
  
  • Common - irregular periods, weight loss, hot flashes
  • Rare / serious - stroke / PE; slight ↑ risk of endometrial cancer (partial ag); vision disturbances
  • Possibly CI in pregnancy / breastfeeding → may induce bone growth plate closure

Question 5

Anti-Estrogens drugs

Answer 5

1. Tamoxifen
2. Toremifene
3. Fulvestrant

Question 6

• Fulvestrant
  
  • MOA
  • Indications
  • Side effects

Answer 6

• Fulvestrant
  • MOA: an ER antagonist - specifically a SERD (degrader), makes ER hydrophobic, unstable + misfolded
  • Indications: ER+, HER2- breast cancer (advanced or metastatic cases; given i.m.)
  • Side Effects:
    
    • Very common - nausea; injection site rxns; ↑ LFTs
    • Less common - UTIs, HS rxns, venous thrombi, vomiting, diarrhea, HA

Question 7

Aromatase inhibitor drugs

Answer 7

1. Anastrozole
2. Letrozole
3. Exemestane

Question 8

• Anastrozole, Letrozole and Exemestane
  
  • MOA
  • Indications
  • Side effects

Answer 8

Anastrozole, Letrozole and Exemestane

• MOA: reversible competitive aromatase inhibition → ↓ peripheral conversion of androgens to estrogens
• Indications: tamoxifen-resistant breast cc. (ER+) in postmenopausal women (periph. E production)
• Side Effects:
  
  • Common - hot flashes, joint pain, nausea, mood alterations
  • Severe / rare - ↑ risk of heart disease and osteoporosis (may co-admin bisphosphonates)
  • CI in premenopausal women, esp. pregnancy; known to cause harm to fetus

Question 9

GnRH analogs drugs

Answer 9

1. Goserelin
2. Buserelin

Question 10

• Goserelin and Buserelin
  
  • MOA
  • Indications
  • Side effects

Answer 10

Goserelin and Buserelin

• MOA: continuous (not pulsatile) s.c. admin → inhibited secretion of gonadotropins (FSH/LH) → ↓ E / T
• Indications: usually in advanced cases of prostate cc. (both) and breast cc. (goserelin only)
• Side Effects:
  
  • “Tumor flare” - transient sx ↑ due to initial LH surge; bone pain, breast pain/swelling, etc.
    
    • prevent with anti-androgen co-admin
  • Sexual dysfunction - erectile dysfunction, ↓ libido

Question 11

Antiandrogen drugs

Answer 11

1. Flutamide
2. Nilutamide
3. Bicalutamide**

Question 12

• Flutamide, Nilutamide and Bicalutamide**
  
  • MOA
  • Indication
  • Side effects

Answer 12

Flutamide, Nilutamide and Bicalutamide**

• MOA: non-steroidal antiandrogens (NSAA) → competitive atg of androgen receptors
  
  • often given with continuous GnRH analogs for
• Indication: prostate cc. (often in combo with GnRH analogs)
• Side Effects:
  
  • Androgen-deprivation effects → gynecomastia, ↓ muscle/bone mass/libido, depression
  • GI effects - nausea, vomiting, diarrhea, anorexia
  • Urine discoloration - blue/green

Question 13

• Corticosteroids
  
  • Drug
  • Indication

Answer 13

Prednisolone - induces apoptosis in lymphomas (via immunosuppressive effects)