Endocrine cancer

Question 1

Name all the drugs and the cancers they treat

Answer 1

Breast cancer: Tamoxifen
Cervical cancer: Pembrolizumab
Prostate cancer: leuprorelin and bicalutamide

Question 2

Which is the major metabolic pathway of tamoxifen? What is the metabolite produced?

Answer 2

N-demethylation (catalysed by CYP3A4)

Major metabolite: N-desmethyl tamoxifen

Question 3

Which is the minor metabolic pathway of tamoxifen? What are the metabolites produced?

Answer 3

Catalysed by CYP2D6

Minor metabolites: 4-OH-tamoxifen and endoxifen (greater affinity for estrogen receptor than tamoxifen)

Question 4

Elaborate on the stereoisomers of tamoxifen and their type of activity

Answer 4

Cis-isomer: estrogenic activity
Trans-isomer: anti-estrogenic activity

Question 5

ADEs of tamoxifen?

When happens at high dose?

Answer 5

• Hot flashes*
• ↑ risk of endometrial cancer*
• Venous thromboembolic events (deep vein thrombosis, DVT)*
• Menstrual irregularities
• Vaginal bleeding and discharge
• N/V

High dose:
acute neurotoxicity (tremor, hyperreflexia, unsteady gait, dizziness)

Question 6

What are the drug-food interactions that can affect the CYP3A4 (major) metabolism pathway of tamoxifen?

Answer 6

Grapefruit and grapefruit juice

Question 7

What are the DDIs that can affect the CYP2D6 (minor) metabolism pathway of tamoxifen?

Answer 7

Diphenhydramine (cough & cold) and SSRIs can inhibit CYP2D6

Question 8

MOA of pembrolizumab for cervical cancer?

Answer 8

PD-1 blocker, binds to PD-1 on T cells → prevents Tcell activities from being suppressed

Question 9

Dose of pembrolizumab for cervical cancer?

Answer 9

IV 200mg every 3w

Question 10

ADEs of pembrolizumab for cervical cancer?

Answer 10

• Infusion-related SEs (rash, itchiness)*
• Life-threatening immune-related inflammation (lung, endocrine organs, liver, kidney, sepsis) *

Others:
- Fatigue
- Diarrhoea
- Nausea
- Joint pain

Question 11

Contraindications for pembrolizumab for cervical cancer?

Answer 11

• Pregnant women → may ↑ risk of miscarriage
• Pts with history of severe reaction (eg hypersensitivity) to Ab therapy
• Pts with illnesses (eg infection, liver/kidney diseases etc) → consult Drs

Question 12

DDIs with pembrolizumab for cervical cancer?

When can they be used?

Answer 12

Immunosuppressants (eg corticosteroids)

• Must be stopped before taking pembrolizumab
• May be used after starting pembrolizumab to deal with immune-related ADEs

Question 13

What are the forms of administration for leuprorelin and bicalutamide for prostate cancer?

Answer 13

Leuprorelin: SC, IM Bicalutamide: PO

Question 14

MOA of leuprorelin for prostate cancer?

Answer 14

Agonist at pituitary GnRH receptors → continuous administration inhibits FSH and LH release → suppress androgen synthesis

Question 15

What should we monitor for a pt on leuprorelin for prostate cancer?

Answer 15

• Prostate-specific antigen (PSA) in the first few weeks
• LH, FSH, testosterone levels after 4w of Tx

Question 16

SEs of leuprorelin for prostate cancer?

Answer 16

• Hot flushes during first few weeks of Tx*
• Altered mood (counsel pt and family members)*
• Hyperglycemia*
• Decreased libido*

Others:
- Local pain and redness @ injection site
- Headache/ dizziness
- GI disturbances

Question 17

Contraindications for leuprorelin for prostate cancer?

Answer 17

• Hypersensitivity
• Pre-existing heart disease
• Pts with risk for osteoporosis

Question 18

MOA of bical?

Answer 18

Androgen Receptor (AR) antagonist

Question 19

What do we use bicalutamide for prostate cancer in combination with?

Why can’t we use it as monoTx?

Answer 19

In conjunction with GnRH analogue to alleviate the effects of testosterone surge that occurs with GnRH agonist initially

Cannot be used as monoTx as block AR → ↑LH secretion → higher testosterone levels

Question 20

Which is the active stereoisomer of bicalutamide for prostate cancer?

How is the active stereoisomer metabolised?

Answer 20

R (active)
S (inactive)

R active stereoisomer metabolised by CYP3A4

Question 20

ADEs of bicalutamide for prostate cancer?

Answer 20

• Hot flushes*
• ↓ Sexual desire/ ability*
• Mild swelling ankles/ legs/ feet*

Others:
- N/V
- Fatigue
- Constipation/ diarrhoea