Anti Cancer Therapies Flashcards
(42 cards)
Cancer Drugs
-Tamoxifen
-Letrozole
-CDK4/6 inhibitors (eg palbociclib)
-Exemestane
-Goserelin
-Trastuzumab
-Imatinib
-Rituximab
-Capecitabine
-Zolendronic acid
-Pembrolizumab
Mechanism of Tamoxifen
-SERM (Selective Oestrogen Receptor Modulator)
-Acts on oestrogen receptors
=Can act in an oestrogenic way or an anti-oestrogenic way, depending on the tissue
-Active in many tissues including breast, uterus, bone, liver, hypothalamus
=Breast: acts as an oestrogen receptor ANTAGONIST, i.e. anti-oestrogen activity
=Uterus: acts as an oestrogen-receptor agonist, which can cause endometrial hyperplasia - increased risk of uterine malignancy
=Bone: acts as an oestrogen-receptor agonist; inhibiting osteoclasts and therefore protecting against osteoporosis
-Requires metabolism in the liver by CYP450 enzymes to convert into the active form
Indications of Tamoxifen
-Adjuvant treatment of ER positive breast cancer in pre-and post- menopausal women
=Early breast cancer
=Metastatic breast cancer
-Treatment of ER positive breast cancer in men
-(Primary prevention of breast cancer in women with a very strong family history)
Tamoxifen side effects
-Hot flushes in approx. 50%
-PV bleeding
-Fatigue
-Weight gain
-Less common
=Anaemia, cataracts, changes in LFTs, alopecia, elevated triglycerides
-SSRIs such as sertraline, paroxetine & fluoxetine decrease plasma level of tamoxifen (SSRIs inhibit CYP2D6 inhibitors so can prevent formation of active drug)
Main serious toxicities of Tamoxifen
-Increased risk of thrombotic disease
=Avoid if personal or family history of VTE; stop if clot
-Endometrial cancer (vaginal bleeding & polyps)
=Counsel patients
=Ix any new/changing PV symptoms early with gynae ref
-Avoid in pregnancy and breast feeding
-Radiation Recall dermatitis (rare!)
Mechanism of letrozole
-Aromatase Inhibitor
=Aromatase catalyses the last steps of oestrogen synthesis from androgens, transforming: Androstenedione to oestrone then Testosterone to oestradiol
=Competitively and reversibly binds to heme portion of cytochrome P450 unit of the aromatase enzyme= Inhibits the activity of aromatase= results in reduced levels of plasma oestrogen
Main source of oestrogen in pre-menopausal women is ovarian
-In post-menopausal women, most of the body’s oestrogen is produced via conversion of androgens into oestrogens by aromatase enzymes in peripheral tissues
Indications of letrozole
-Neo-adjuvant treatment: in post menopausal women with ER positive cancer pre-operatively
-Adjuvant treatment
=Post-menopausal women with ER+ early breast Ca
=High risk pre-menopausal women with ER+ early breast Ca (+ LHRH analogue)
-Palliative treatment: in metastatic disease - post-menopausal women with ER+ breast Ca
Common side effects of letrozole
-Myalgia & arthralgia (~70-80%)!!!
-Bone pains
-Hypercholesterolaemia
-Headaches
-Hot flushes, nausea
-Depression
-Alopecia
-Osteoporosis risk
-Avoid in renal impairment
Mechanism of exemestane
-Steroidal aromatase inhibitor
-Suppresses synthesis of oestrogen; same MOA as letrozole
-BUT greater androgenic effect - so less hair thinning & assoc SEs
Indications of Exemestane
-Adjuvant treatment of ER positive early breast cancer in post menopausal women (or pre-menopausal with ovarian blockade)
-Alternative to letrozole if adverse effects
-Metastatic disease/palliative setting for disease control
Drug interactions of Exemestane
CP450 inducers reduce the bioavailability of exemestane
Common side effects of Exemestane
-Hot flushes and sweating (10%)
-Arthralgia
-Osteoporosis (note this is steroidal, so additional impact on bone mineral density)
Serious side effects of Exemestane
-Deranged LFTs
-Acute generalised exanthematous pustulosis (AGEP) (also called Toxic Pustuloderma in some books)
=Uncommon pustular drug eruption
=Classified as a severe cutaneous adverse reaction
Mechanism of Goserelin
-LHRH (luteinizing hormone-releasing hormone) agonist
-Also known as LNRH analogue or Gonadotropin-releasing hormone (GnRH)
-LHRH is produced in the hypothalamus
-Synthetic analogue of LHRH
-Initial phase of stimulation (FLARE) with initial release of FSH & LH
—>down regulation of gonadotrophin-releasing hormone receptors
—> desensitisation of pituitary to gonadotrophin-releasing hormone
—> decreased secretion of LH & FSH from pituitary
-SO:
=Reduction of gonadotrophin release
=Inhibition of androgen and oestrogen production
Licensed indications for Zoladex
-Prostate Cancer
=Neo-adjuvant (prior to XRT)
=Adjuvant (post XRT or radical prostatectomy)
=Metastatic setting
-Breast Cancer
=Pre menopausal women as adjuvant treatment
=Advanced breast cancer
-Gynaecology
=Endometriosis
=Pre op in women with fibroids and anaemia
=Fertility treatments
Drug interactions/ contraindications of Zoladex
-Undiagnosed vaginal bleeding
-Prostate cancer patients at risk of:
=MSCC
=Ureteric obstruction
-Caution in
=Diabetes/hypertension
Common toxicities of Zoladex
-Arthralgia and bone pain
-Gynaecomastia
-Heart failure
-Hot flushes
-Hyperhidrosis
-Sexual dysfunction: decreased libido, impotence
-Altered mood
Serious side effects of Zoladex
-Tumour Flare
=MSCC
=Ureteric obstruction
-Psychotic disorder
Mechanism of action of Herceptin/ Trastuzumab
-Monoclonal antibody that targets HER2 receptors expressed on the surface of some breast and gastric cancers
—> inhibits HER2 signalling pathways
—> induces apoptosis
-HER2 receptors are transmembrane receptors that have a key role in the signalling network that drives cell proliferation
-A monoclonal antibody targeting HER2.
-The HER2 pathway promotes cell growth and division when it is functioning normally; however, when it is over expressed, rapid cell growth and proliferation occur tumour formation and growth. Trastuzumab induces an immune-mediated response that down regulates HER2
Licensed indications of Herceptin
-Early breast cancer that over expresses human epidermal growth factor 2 (HER2). This is approximately 20-30% of all early breast cancers
=Neo adjuvant
=Adjuvant
-Metastatic HER2 positive breast cancer
-Metastatic HER2 positive gastric cancer
Common side effects of Herceptin
-Angioedema
-Infusion related reaction (50%)
-Flu like symptoms (very common!)
-Nausea
Serious toxicities and drug interactions of Herceptin
-Severe infusion related reaction
-Thrombocytopaenia
-Cardiac toxicity:
=In 2-7% of patients, trastuzumab is associated with cardiac dysfunction, which includes congestive cardiac failure.
=Co-administration with anthracycline chemotherapy (-rubicin) increase this risk
=How do we monitor cardiac function? What specifically are we monitoring?
-Harmful to foetus
Mechanism of action of Imatinib (Glivec)
-Targeted therapy, given orally
-Tyrosine kinase inhibitor
-Tyrosine kinases are important mediators of the cell signalling cascade. They phosphorylate tyrosine residues(phosphorylation – addition of a phosphate group)
-Tyrosine kinase inhibitors acts by inhibiting cell proliferation
Licensed indications of Imatinib
-Treatment of Chronic Myeloid Leukaemia (CML)
-Treatment of Philadelphia positive
Acute Lymphoblastic Leukaemia (ALL)
-Adjuvant treatment of high risk GIST
