8.3.4 Hormone antagonists

8.3.4.1 Breast cancer

Drugs for the endocrine therapy of breast cancer

Endocrine therapies are commonly used in the management of patients with oestrogen receptor–positive breast cancer. Neo–adjuvant endocrine therapy may be given to postmenopausal women for at least 3 months to down–stage locally advanced tumours before definitive local treatment with surgery or radiotherapy. Adjuvant endocrine therapy is given for 5 to 9 years after local treatment, to reduce the risk of relapse. In metastatic disease, endocrine therapy is continued until the disease progresses. The sequential use of endocrine therapies may control metastatic disease for lengthy periods in oestrogen–receptor positive breast cancer.
(a) neo–adjuvant therapy of postmenopausal breast cancer

(given for at least 3 months prior to surgery or radiotherapy)

First Choice:
letrozole
Second Choice:
tamoxifen
(b) adjuvant therapy of early breast cancer (specialist will determine choice of regime)

Pre- or peri-menopausal breast cancer
First Choice:
tamoxifen

Post-menopausal breast cancer

Low risk of recurrence
First Choice:
tamoxifen (for 5 years)
Risk of early recurrence (or contraindication to tamoxifen)
First Choice:
letrozole (for 5 years)
Second Choice:
anastrazole (for 5 years)
Risk of late recurrence
First Choice:
tamoxifen (for 5 years)
then letrozole (for 4 years)
(c) metastatic breast cancer (continued until the disease progresses)

No prior adjuvant tamoxifen
First Choice:
letrozole
Second Choice:
tamoxifen
Prior adjuvant tamoxifen
First Choice:
letrozole
Second Choice:
exemestane
Formulations/Dose

Endocrine therapy must only be initiated on the advice of a hospital specialist.

  • tamoxifen tablets 20mg: 20mg daily.
  • letrozole tablets 2.5mg: 2.5mg daily.
  • anastrozole tablets 1mg: 1mg daily.
  • exemestane tablets 25mg: 25mg daily.
  • goserelin implant 3.6mg: 3.6 mg by subcutaneous injection every 28 days.
Prescribing Notes
  • The aromatase inhibitors letrozole, anastrozole and exemestane are ineffective in premenopausal women unless concomitant goserelin is given to suppress ovarian function. Letrozole plus goserelin may be given where there is a contraindication to tamoxifen in pre-menopausal women.
  • Tamoxifen is more effective when ovarian function is suppressed in premenopausal women. Concomitant goserelin may be given for the first two years of adjuvant tamoxifen therapy in patients with a high risk of recurrence.
  • Oophorectomy is an alternative to goserelin in premenopausal women.
  • Tamoxifen increases the risk of venous and arterial thrombosis. Letrozole or anastrozole should be used in patients with an increased risk of thromboembolism.
  • Tamoxifen increases the risk of endometrial cancer. Abnormal vaginal bleeding should be investigated promptly.
  • Patients who are peri-menopausal at initiation of adjuvant endocrine therapy and who have completed 2-3 years of tamoxifen may be switched to exemestane for the remainder of the 5 years on the recommendation of the specialist.
  • Endocrine therapy may cause a transient increase in bone pain in patients with bony metastases.
  • Goserelin is appropriate for a shared care arrangement to facilitate the seamless transfer of individual patient care from secondary care to general practice.
8.3.4.2 Prostate cancer and gonadorelin analogues
Endocrine therapies are commonly used in the management of patients with prostate cancer. Neo–adjuvant endocrine therapy may be given for up to 3 months to down–stage locally advanced tumours before definitive local treatment with radiotherapy. Locally advanced prostate cancers unsuitable for local therapy may be treated by a gonadorelin analogue, or by bicalutamide alone in younger men who wish to retain potency. Gonadorelin analogues are also used in metastatic prostate cancer, with initial anti–androgen cover to prevent tumour flare, and the combination of a gonadorelin analogue and an anti–androgen is used to provide maximal androgen blockade in second–line treatment of metastatic disease. 

Endocrine therapy must only be initiated on the advice of a hospital specialist

Anti–androgen
First Choice:
bicalutamide
Second Choice:
flutamide
Gonadorelin analogues
First Choice:
leuprorelin Prostap® DCS
Second Choice:
goserelin
ortriptorelin
Formulations/Dose

Endocrine therapy must only be initiated on the advice of a hospital specialist.

  • bicalutamide tablets 50mg, 150mg: to prevent tumour flare when a gonadorelin analogue is started, 50mg daily for 3 weeks starting 2 weeks before the gonadorelin analogue. Used as a single agent for locally advanced disease, 150mg daily. Administered concurrently with a gonadorelin analogue to obtain maximum androgen blockade, 50mg daily.
  • flutamide tablets 250mg: 250mg three times daily.
  • leuprorelin (Prostap® SR DCS) 3.75mg powder and solvent for prolonged release suspension for injection in pre-filled syringe: 3.75mg every month.
  • leuprorelin (Prostap® 3 DCS) 11.25mg powder and solvent for prolonged release suspension for injection in pre-filled syringe: 11.25mg every three months.
  • triptorelin injection m/r 3mg vial (with diluent): by intramuscular injection, 3mg every 4 weeks.
  • triptorelin injection m/r 11.25mg vial (with diluent): by intramuscular injection, 11.25mg every 3 months.
  • triptorelin injection m/r 22.5mg vial (with diluent): by intramuscular injection, 22.5mg every 6 months
  • goserelin prefilled syringe 3.6mg, 10.8mg: by subcutaneous injection, for neo–adjuvant therapy, 3.6mg every 4 weeks for 3 months. For longer term treatment of locally advanced or metastatic disease, 10.8mg subcutaneously every 3 months. An anti–androgen should be started 2 weeks before goserelin to prevent tumour flare, and continued for 3 weeks in total.
Prescribing Notes
  • There are differences in the licensing of individual agents; please refer to the Summary of Product Characteristics.
  • Gonadorelin analogues cause side–effects similar to orchidectomy. Both anti–androgens and gonadorelin analogues may cause gynaecomastia, reduced libido, hot flushes, mood changes and sweats.
  • Gonadorelin analogues may cause ‘tumour–flare’ in the first weeks of treatment with a transient worsening of pain or ureteric obstruction. This can be prevented by pre–treatment with an anti–androgen.
  • Bicalutamide is the first choice of anti–androgen because of its once daily administration schedule. It should not be used as monotherapy for the treatment of localised prostate cancer, but it is licensed for monotherapy of locally advanced prostate cancer.
  • Cyproterone may be used to treat hot flushes associated with gonadorelin analogues.
  • Degarelix (Firmagon®) is a gonadotrophin-releasing hormone antagonist approved for Specialist Use only for the treatment of advanced hormone-dependent prostate cancer.  It should be used only for those who are at risk of spinal cord compression.

8.3.4.3 Somatostatin analogues

Neuroendocrine tumours

Short-acting

First Choice:
octreotide
Long-acting
First Choice:
lanreotide
Second Choice:
octreotide depot (Sandostatin LAR®)
Acromegaly
First Choice:
octreotide
orlanreotide
Formulations/Dose

Treatment should only be initiated on the advice of a hospital specialist

  • octreotide injection 50micrograms/mL, 100micrograms/mL, 200micrograms/mL, 500micrograms/mL: by subcutaneous injection;
      for treatment of carcinoid syndrome, initially 50micrograms once or twice daily, gradually increased according to response to 200micrograms three times daily
      acromegaly, short-term treatment before pituitary surgery or long-term treatment in those inadequately controlled by other treatment or until radiotherapy becomes fully effective, 100-200micrograms three times daily; discontinue if no improvement within 3 months.
  • octreotide (Sandostatin LAR®) depot injection 10mg, 20mg, 30mg:
      neuroendocrine (particuarly carcinoid) tumour adequately controlled on subcutaneous octreotide, by deep intramuscular injection into gluteal muscle, initially 20mg every 4 weeks, for 3 months then adjusted according to response; max 30mg every 4 weeks.  Continue subcutaneous octreotide for 2 weeks after first dose of depot
      acromegaly in patients adequately controlled on subcutaneous octreotide, by deep intramuscular injection into gluteal muscle, initially 20mg every 4 weeks for 3 months, then adjusted according to response; max 30mg every 4 weeks.  Start depot octreotide 1 day after the last dose of subcutaneous octreotide.
  • lanreotide injection 30mg (Somatuline® LA): by intramuscular injection, acromegaly and neuroendocrine (particularly carcinoid) tumours, initially 30mg every 14 days, frequency increased to every 7 – 10 days according to response.
  • lanreotide 60mg, 90mg, 120mg in prefilled syringe (Somatuline Autogel®): by deep subcutaneous injection into the gluteal region;
      acromegaly (if somatostatin analogue not given previously), initially 60mg every 28 days, adjusted according to response; for patients treated previously with a somatostatin analogue, consult product literature for initial dose, dose to be given in the gluteal region.
      Neuroendocrine (particularly carcinoid) tumours, initially 60-120mg every 28 days, adjusted according to response.
Prescribing Notes
  • Somatostatin analogues are used for the relief of symptoms associated with neuroendocrine tumours, particularly carcinoid syndrome.
  • Thyroid function should be checked every 12 months.
  • Treatment may cause diarrhoea.
  • Somatostatin analogues for neuroendocrine tumours and octreotide in acromegalic patients are appropriate for a shared care arrangement to facilitate the seamless transfer of individual patient care from secondary care to general practice.
  • The primary treatment of acromegaly is usually pituitary surgery.  Management and treatment requires specialist involvement.

  • Pasireotide is approved for use in patients with acromegaly for whom surgery is not an option or has not been curative and who are inadequately controlled on treatment with another somatostatin analogue.