ic10 endocrine cancer drugs

Question 1

What is Tamoxifen used for?

MOA of Tamoxifen

Answer 1

Breast cancer

MOA: Competitively blocks endogenous estrogen binding to estrogen receptor → Alter gene expression, prevent cell activation and proliferation

Question 2

Benefits of Tamoxifen (other than treatment for breast cancer, 2 points)

Answer 2

Chemoprevention of breast cancer in high risk women

Can reduce severity of osteoporosis (but not 1st line)

Question 3

Which Tamoxifen isomer as anti-estrogenic activity

Answer 3

Trans isomer

Question 4

Why does Tamoxifen have a high Vd?

Answer 4

Tamoxifen concentrates tissues eg. in breast, uterus, liver, kidney, lung, pancreas, ovary

2-3x in uterus, 10x in breast VS in circulation

Question 5

What is the major metabolic pathway of Tamoxifen?

What is produced?

Answer 5

CYP3A4 → CYP2D6

Undergo N-demethylation to form N-demethyl-Tamoxifen

Eventually produces Endoxifen (most active metabolite)

Question 6

What is the minor metabolic pathway of Tamoxifen?

What is produced

Answer 6

CYP2D6 → CYP3A4

Produces 4-OH Tamoxifen (active metabolite)

Eventually produces Endoxifen (most active metabolite)

Question 7

Which pathway of Tamoxifen metabolism produces an intermediate active metabolite?

What is the name of the intermediate active metabolite?

Answer 7

Minor pathway (CYP2D6 → CYP3A4)

4-OH Tamoxifen

Question 8

DDI with Tamoxifen (2 points)

Answer 8

CYP3A4 inhibitors: Grapefruit juice

CYP2D6 inhibitor: Diphenhydramine
Will result in increased activity cos of active intermediate metabolite

Question 9

Side effect of Tamoxifen (5 points)

Hint: related to Hormonal contraceptives (maybe due to increased estrogen level in the body cos blocking their binding to androgen receptor?)

Answer 9

Hot flushes
Increase risk of endometrial cancer
DVT
Menstrual irregularities
Vaginal bleeding, discharge

Question 10

Common side effects of all the drugs in IC10

Answer 10

Hot flushes

Question 11

What is Pembrolizumab?

Answer 11

Immune checkpoint inhibitor, for cervical cancer

Question 12

MOA of Pembrolizumab

Answer 12

Block PD-L1 receptor on T cell, receptor cannot bind to PD-L1 on Tumour cells, and will kill them

PD-L1 receptor binding to PD-L1 on tumour cells would not kill cell

Question 13

How is Pembrolizumab administered?

Answer 13

IV infusion over 30 mins

Question 14

What is the life threatening reaction associated with Pembrolizumab

Answer 14

Immune-related inflammation on lungs, endocrine organs, liver, kidney, sepsis

Question 15

Contraindicated patients in Pembrolizumab

Answer 15

Taking corticosteroids or immunosuppressants

Pregnant women

History of severe reaction to other antibody therapy

Question 16

What are the drugs / therapy used in Prostate cancer? (4 points)

Answer 16

Leuprorelin
Finasteride
Bicalutamide
Surgical castration

Question 17

MOA of Leuprorelin

Answer 17

Act as GnRH, bind to GnRH receptor continuously and cause Pituitary to produce lesser FSH and LH

Question 18

Contraindication with Leuprorelin

Answer 18

Heart disease
Patients at risk for osteoporosis

Question 19

MOA of Bicalutamide

Answer 19

Androgen receptor (AR) antagonist
Bind to AR, prevent AR from entering nucleus and prevent DHT from binding to AR

Question 20

Can Bicalutamide be used for monotherapy? Why?

Answer 20

No. Solely blocking AR will increase LH secretion → resulting in higher testosterone levels

Should be used with Leuprorelin (decreases LH secretion)

Question 21

Which isomer is active for Bicalutamide

Answer 21

R isomer

Question 22

Side effect of Bicalutamide (4 points)

Answer 22

Hot flushes
Decreased libido
Constipation
Mild swelling of ankles