CPT: Endocrine therapy Flashcards
Naturally occurring hormones can stimulate the growth and proliferation of some cancers. What are examples of these?
There is a long duration of treatment:
- Adjuvant (after surgery) to prevent recurrence
- Breast cancer ~ 10 years
- Prostate cancer ~ 3 years
- For advanced cancers until disease progression
- In advanced and metastatic cancer, hormone therapy is often given until it is no longer effective which is usually referred to as disease progression
How do Hormone therapies work to treat these types of cancers?
Reducing the level of hormones reaching cancer cells or Blocking the action of these hormones on cancer cells
What is the length of treatment for these cancers? When can be treatment be given and how long typically for?
There is a long duration of treatment: Adjuvant (after surgery) to prevent recurrence For advanced cancers until disease progression
Hormones are also used in neuroendocrine cancer tumours which are rarer than prostate and breast cancer but you may still come across in practice.
What is an example of hormones/ analogues used - how does it work and why?
Somatostatin analogues such as octreotide and lanreotide are used to relieve the symptoms of neuroendocrine tumours, including hormone-secreting tumours of the gastrointestinal tract.
These tumours express somatostatin receptors, Somatostatin is a naturally occurring inhibitory hormone activation of which inhibits cell proliferation as well as hormone secretion
75% of breast cancer tumours are ?
What does this mean?
75% of breast cancer tumours are (oEstrogen Receptor) ER+
This mean when oestrogen attaches to ER on surface of the tumour it stimulates growth an proliferation
Where pre and post menopause is the main producer of oestrogen?
- Pre-menopause, ovaries main producer of oestrogen
- Post-menopause, adipose tissue main source
- Determines choice of therapy
- Opportunity for lifestyle intervention
- Explains link between obesity & breast cancer – help encourage lifestyle advice & referral to dietricain
Apart from life-style what treatment option can be used?
Ovarian Suppression can also be used
- Chemotherapy (induces temporary or permanent ovarian suppression)
- Gonadotrophin-releasing hormone analogues e.g. goserelin, leuprorelin, triptorelin used in premenopausal breast cancer
- Surgery (Oophorectomy)
- Not routinely considered – but might be for preventing women with BRCA gene at high risk
Tamoxifen is a drug used for treatment in breast-cancer
What is its mechanism of action?
Complex mechanism of action, acts primarily as an oestrogen antagonist therefore prevents oestrogen binding to the oestrogen receptors in tumour
- …and in normal tissue leading to symptoms associated with menopause
When is tamoxifen used?
When is it most effective?
- Used pre and post-menopause
- When used for 10 years after surgery to reduce risk of recurrence
What interactions does tamoxifen have?
- Interactions - cytochrome P450
- SSRI’s
- Important role for pharmacists
Tamoxifen is metabolised by cytochrome P450 system of enzymes and therefore carries a risk of interacting with other drugs metabolised by this group.
What is the mechanism of action of
- Fulvestrant is a competitive oestrogen receptor (ER) antagonist and leads to the downregulation of oestrogen receptor protein levels.
- Unlike tamoxifen does not have agonist activity
When is Fluvestrant used?
- Second line endocrine therapy for relapsed disease on first-line endocrine therapy
- It is also recommended in combination therapy with CDK4/6 inhibitors
What route, dose and frequency is fluvestrant taken?
•2 x 250mg slow IM injections each month – one delivered into each buttock
How do aromatase inhibitors work?
When can they be used?
What are examples?
- In post-menopausal women oestrogen is primarily produced by adipose and muscle tissue
- Aromatase inhibitors block the aromatisation process in adipose tissue responsible for conversion of androgens into oestrogens. This therefore reduces level of oestrogen available to stimulate cancer cells
- Letrozole, Exemestane, Anastrozole
- Check local formulary for choice
Side effects and maangement - read
What are common side effects of endocrine therpay/ menopausal symptoms?
- Hot flushes and night sweats
- Vaginal dryness, changes to libido
- Heart palpitations
- Mood changes, difficulty sleeping, anxiety, irritability
- Memory and concentration problems
- Joint pain
- Changes to skin, thinning hair
- Weight gain, particularly around the waist
- Breast Cancer Now Discussing Menopausal Symptoms
- https://youtu.be/GyMpbiaM_Os
What are treatments for menopausal side effects?
- Aimed at the individual symptoms
- Pharmacological and non-pharmacological interventions (CBT)
- Low dose SSRI, SNRI, gabapentin, clonidine
- Used for vasomotor symptoms (hot flushes)
- Off label, refer to NICE CKS for guidance
- Also affective disorders due to diagnosis – may also have depression & anxiety
- Vaginal moisturisers – for vaginal dyness
- Complementary therapy and lifestyle interventions
- Breast Cancer Now, Maggie’s and Macmillan
- Herbal medicines (Black Cohosh) should be avoided
What stimulates prostate cancer cells to grow and divide?
Testosterone
What is cancer treatment for prostate cancer called?
What does it aim to do?
•Hormone therapy aka Androgen Depletion Therapy aims to:
- •Lower the risk of recurrence with early prostate cancer
- •Shrink or slow advanced cancer
What are the 2 mechanisms by which andorgen depletion therapy can work?
- Blocking androgen receptors (anti-androgens)
- Bicalutamide
- Enzalutimide
- Lower testosterone levels
- Luteinising hormone releasing hormone (LHRH) agonists
- Gonadotrophin releasing hormone (GnRH) antagonsits
- Abiraterone
Prostate cancer divided into 2 different categories which helps influence which therapy used.
What are these?
Castrate sensitive disease or Castrate – resistant prostate cancer
- Prostate Cancer which responds to hormone therapy is considered castrate sensitive disease.
- Castrate-resistant prostate cancer (CRPC) is defined by disease progression despite androgen depletion therapy (ADT) and may present as either a continuous rise in serum prostate-specific antigen (PSA) levels, the progression of pre-existing disease, and/or the appearance of new metastases.
Describe the normal hypothalamic–pituitary–adrenal axis.
Normal Hormonal feed-back In men/women:
WOMEN:
Hypothalamus produces Gonadotrophin releasing hormone (GnR). This stimulates anterior pituitary to release LH and FSH. These stimulate the development of the follicles in the ovaries. Follicles release ostrogen – which has a negative feed-back effect on the hypothalamus & anterior pituitary gland.
MEN:
Hypothalamus produces Gonadotrophin releasing hormone (GnR). This stimulates anterior pituitary to release LH. This acts on the testicals to produce testosterone which has a negative feed-back effect on the hypothalamus & anterior pituitary gland.
How do GnRH analogues work?
- These are agonists of GnRH receptors on the anteioir pituitary gland.
- Activation of the GnRH receptors stimulates LSH and FSH to have a very large release.
- This stimulates ovaries/testicles to release a lot of ostrogen/ testosterone for a few days (worsens symptoms of cancer).
- Given as SC/IM which has a slow release over 1-3 months
- After continuous stimulatous – these receptors become densisitised. This prevents these receptors action therefore lowers Testosterone/ oestrogen levels.
- Over time they will become sensitized again therefore dose needs to be given regularly to prevent this.
What are examples of GnRH analogues?
What is there route of admin and duration?
What can also be used along side to reduce effects of flare?
- GnRH analogues: Goserelin, leuprorelin and triptorelin
- Differ in method of administration (IM, SC)
- Duration of action (1 – 6 months)
- Check local formulary and guidelines
- Transient increase in testosterone levels (“flare”) for 7-10 days
- Usually start an anti-androgen 3 days before LHRH (bicalutamide, cyproterone) to minimise effects
What is an example of Gonadotrophin release hormone antagonist?
How does it work?
Routem dose, frequency?
- Degarelix
- Competitively and reversibly binds to the pituitary GnRH receptors
- Reduces release of gonadotrophins (LH/FSH) which halts the secretion of testosterone by the testes
- No tumour flare
- 2 x 120mg SC injections then 80mg each month
Side effects of prostate cancer treatment
What is the mechanism of action of Abiraterone?
Side effects?
Monitoring requirement?
- Inhibits CYP17 to block androgen synthesis in testicular, adrenal and prostatic tumour tissues
- CYP17 catalyses the conversion of pregnenolone and progesterone into testosterone precursors by 17α-hydroxylation and cleavage of the C17,20 bond
- CYP17 inhibition also results in increased mineralocorticoid production by the adrenals leading to side effects:
- Hypertension, hypokalaemia, oedema
- Requires concurrent prednisolone (10mg daily)
- Baseline blood pressure and cardiac function then monthly BP
- FBC, U&Es, LFTs & PSA prior to each cycle
Abiraterone counselling points
- •Swallow 2 x 500mg tablets whole, with water one hour before and at least two hours after eating
- •Consumption with food increase absorption by up to 10 times
- •Patients with increased stress (e.g. admission to hospital) require additional steroid supplementation
•Interactions:
- •CYP2D6: propranolol, venlafaxine, haloperidol, risperidone, flecainide, codeine, oxycodone, tramadol
- •Inhibits CYP2C8 (pioglitazone) - switch antiepileptic drug
- •Strong CYP3A4 inducers (such as phenytoin, carbamazepine, rifampicin, St John’s wort) may reduce abiraterone effectiveness. - stop taking these?
How does enzalutimide work?
Dose, frequency, route?
Side effects?
Interactions?
Monitoring?
What is a major side effect of treatment for both breast and prostate cancer?
Treatment?
- Hormone therapy for breast and prostate cancer increase the risk of osteoporosis
- Follow current guidelines for the condition being treated
- Assess individual patients risk of falls and fracture
- Consider:
- Calcium and vitamin D supplementation
- Bisphosphonates
- Denosumab
