Endocrine cancer Flashcards
Name all the drugs and the cancers they treat
Breast cancer: Tamoxifen
Cervical cancer: Pembrolizumab
Prostate cancer: leuprorelin and bicalutamide
Which is the major metabolic pathway of tamoxifen? What is the metabolite produced?
N-demethylation (catalysed by CYP3A4)
Major metabolite: N-desmethyl tamoxifen
Which is the minor metabolic pathway of tamoxifen? What are the metabolites produced?
Catalysed by CYP2D6
Minor metabolites: 4-OH-tamoxifen and endoxifen (greater affinity for estrogen receptor than tamoxifen)
Elaborate on the stereoisomers of tamoxifen and their type of activity
Cis-isomer: estrogenic activity
Trans-isomer: anti-estrogenic activity
ADEs of tamoxifen?
When happens at high dose?
- 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)
What are the drug-food interactions that can affect the CYP3A4 (major) metabolism pathway of tamoxifen?
Grapefruit and grapefruit juice
What are the DDIs that can affect the CYP2D6 (minor) metabolism pathway of tamoxifen?
Diphenhydramine (cough & cold) and SSRIs can inhibit CYP2D6
MOA of pembrolizumab for cervical cancer?
PD-1 blocker, binds to PD-1 on T cells → prevents Tcell activities from being suppressed
Dose of pembrolizumab for cervical cancer?
IV 200mg every 3w
ADEs of pembrolizumab for cervical cancer?
- Infusion-related SEs (rash, itchiness)*
- Life-threatening immune-related inflammation (lung, endocrine organs, liver, kidney, sepsis) *
Others:
- Fatigue
- Diarrhoea
- Nausea
- Joint pain
Contraindications for pembrolizumab for cervical cancer?
- 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
DDIs with pembrolizumab for cervical cancer?
When can they be used?
Immunosuppressants (eg corticosteroids)
- Must be stopped before taking pembrolizumab
- May be used after starting pembrolizumab to deal with immune-related ADEs
What are the forms of administration for leuprorelin and bicalutamide for prostate cancer?
Leuprorelin: SC, IM Bicalutamide: PO
MOA of leuprorelin for prostate cancer?
Agonist at pituitary GnRH receptors → continuous administration inhibits FSH and LH release → suppress androgen synthesis
What should we monitor for a pt on leuprorelin for prostate cancer?
- Prostate-specific antigen (PSA) in the first few weeks
- LH, FSH, testosterone levels after 4w of Tx
SEs of leuprorelin for prostate cancer?
- 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
Contraindications for leuprorelin for prostate cancer?
- Hypersensitivity
- Pre-existing heart disease
- Pts with risk for osteoporosis
MOA of bical?
Androgen Receptor (AR) antagonist
What do we use bicalutamide for prostate cancer in combination with?
Why can’t we use it as monoTx?
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
Which is the active stereoisomer of bicalutamide for prostate cancer?
How is the active stereoisomer metabolised?
R (active)
S (inactive)
R active stereoisomer metabolised by CYP3A4
ADEs of bicalutamide for prostate cancer?
- Hot flushes*
- ↓ Sexual desire/ ability*
- Mild swelling ankles/ legs/ feet*
Others:
- N/V
- Fatigue
- Constipation/ diarrhoea
