Hormonal Therapy

Question 1

Give indications for HT in ovarian cancer

Answer 1

Primary systemic epithelial (adjuvant or maintenance)

• endometrioid (grade 1)
• LGSOC

Recurrent

• epithelial ovarian
• malignant sex cord-stromal tumors

Question 2

What’s the role of HT in uterine cancer?

Answer 2

Uterine cancer

• endometrioid
• endometrial stromal sarcoma
• fertility-sparing option if all criteria are met

Question 3

What are the drug classes for HT?

Answer 3

Question 4

What is the MoA for aromatase inhibitors?

Why do you use AI in postmenopausal women and not pre-menopausal?

Answer 4

AIs block aromatase (enzyme catalyzes the final step in estrogen production)

Why use AI in postmenopausal women only?

• Postmenopausal women:
  
  • primary source of estrogen = peripheral (liver, fat, skin, and breast tissue)
• Premenopausal women:
  
  • primary source of estrogen = ovaries
  • higher levels of circulating androgens compete for the aromatase enzyme complex, resulting in less efficient suppression
  • lower estrogen levels lead to compensatory changes in the ovary, including upregulation of ovarian aromatase enzymes

Question 5

Give examples of AIs.

Give the dosage and administration for AIs.

Answer 5

• Letrozole
• Anastrozole
• Exemestrane

Question 6

Give the MoA of tamoxifen

What’s the dosage?

Answer 6

Tamoxifen binds to estrogen receptors and induce conformational changes blocking or alterating estrogen dependent cancer cell growth

• Antagonist and agonist effects
  
  • antagonist: breast, brain
  • agonist: uterus, bone, lung, and liver
• Dosage
  
  • Tamoxifen (Nolvadex) 20 mg po BID

Question 7

What are drug interactions to be worried about for tamoxifen?

Answer 7

• Antidepressants
• Warfarin

Question 8

What’s the MoA?

Answer 8

• Exact MoA unknown
• Proposed MoA
  
  • Suppression of LH release from pituitary gland
  • Enhancement of estrogen metabolism
  • Promotion of differentiation and maintenance of endometrial tissue

Question 9

List progestins and their dosage

Answer 9

• Megestrol (Megace): 40 mg PO QID or 80 mg PO BID
• Medroxyprogesterone (Depo-Provera) 400 - 1000 mg IM weekly until stabilization, then may reduce to as low as 400 mg IM monthly
• Medroxyprogesterone (Provera) 200 mg PO daily
  
  • available in US as 10 mg tablet
  • not to be used in severe hepatic impairment

Administration

• May be taken without regard to food
  
  • Exception: increased absorption of megestrol suspension when taken with food

Question 10

What’s the MoA of leuprolide?

What’s the dosage of leuprolide?

Answer 10

Leuprolide stimulates GnRH release which results in negative feedback to downregulate receptor and release of FSH/LH.

Leuprolide (Lupron Deport) 3.75 - 7.5 mg IM qMonth OR 11.25 - 22.5 mg IM q3 months

Question 11

What’s the MoA of fulvestrant?

What is the dosage for fulvestrant?

Answer 11

• MoA
  
  • Fulvestrant competitively binds to ER and also causes ER degradation and downregulation
• Dosage
  
  • Fulvestrant (Faslodex) 500 mg IM q2 weeks for 3 doses then qMonth afterwards
    
    • dose-reduce to 250 mg for moderate hepatic impairment (Child-Pugh class B)
    • Not recommended in severe hepatic impairment (Child-Pugh class C)
• Administration
  
  • Two 5 mL syringes, one in each buttock over 1-2 minutes

Question 12

• Rank the highest to lowest incidence of HT responsible for hot flashes
• How do you manage hot flashes?

Answer 12

• AI, tamoxifen, leuprolide > fulvestrant > progestins (minimal)

Question 13

• Rank the highest to lowest incidence of HT responsible for arthralgia and myalgias
• How do you manage arthralgias/myalgias?

Answer 13

• AI > tamoxifen, leuprolide > fulvestrant > progestins (minimal)

Question 14

• Rank the highest to lowest incidence of HT responsible for GI side-effects
• How do you manage GI side effects

Answer 14

• AI, tamoxifen, fulvestrant > progestins > leuprolide (minimal)
• Management
  
  • take oral agents with food
  • anti-emetics

Question 15

• Rank the highest to lowest incidence of HT responsible for vaginal atrophy
• How do you manage vaginal atrophy?

Answer 15

• AI, tamoxifen > leuprolide fulvestrant > progestins (minimal)
• Management
  
  • OTC lubricants and moisturizers
  • Topical estrogen (only in severe cases)

Question 16

Rank the highest to lowest incidence of HT responsible for osteopenia/osteoporosis

How do you manage osteopenia/osteoporosis?

Answer 16

Question 17

Discuss metabolic changes associated wtih HT

Answer 17

Question 18

• Rank the risk of VTE among the HT agents
• What HT agent increases risk of cataracts? Tumor flare?

Answer 18

VTE

• venous (DVT, PE) and arterial (Stroke, MI)
• Tamoxifen, megestrol > AI > leuprolide, fulvestrant, medroxyprogesterone

Cataracts

• Tamoxifen, AI

Tumor flare

• leuprolide, tamoxifen, megestrol

Question 19

What are other side-effects of HT?

Answer 19

• headache
• mood changes
• fluid retention
• insomnia
• liver dysfunction
• injection site reactions (fulvestrant, leuprolide, medroxyprogesterone)