COMMENT

P

rostate cancer (PC) is a considerable healthcare challenge for the UK, being the most common male cancer and the second most frequent cause of death after lung cancer; in 2011, 41 736 men were diagnosed with PC and 10 793 died of the disease (Cancer Research UK, 2014). Diagnosis of PC is more common among black people and those who have a family history of PC. The incidence of PC has also increased with longer life expectancy. Diagnosis is increasingly common thanks to the availability of the prostate-specific antigen blood test (PSA) (European Association of Urology (EAU), 2014). PC is classified into three stages: localised, organ-confined disease; locally advanced, where the cancer has invaded the seminal vesicles or spread beyond the prostate, possibly involving the local lymph nodes; or, advanced disease, where the cancer has spread to other parts of the body such as the skeletal system, distant lymph nodes, and other organs (American Joint Committee on Cancer, 2009). PC is assessed by looking at the patient’s rectal examination, PSA level and histology (EAU, 2014). Treatment for PC depends on its stage and grade, previous pelvic treatment, the patient’s comorbidities, life-expectancy and treatment choice. Testosterone is a male sex hormone (androgen) which is produced by the testes and indirectly by the adrenal glands, being responsible for bone density, muscular development and in puberty, sexual growth. Testosterone stimulates PC cells to grow. Hormone treatment or androgen deprivation therapy (ADT) aims to block the making of androgens by lowering production in the testes. In early PC, ADT will stop recurrence of the disease, and in advance PC, ADT will reduce the size of the tumour and slow down the disease progression. Surgical bilateral or subcapsular orchiectomy is considered a hormone therapy and will reduce testosterone levels by 95 %, but it is disfiguring and unpopular (EAU, 2014). The pituitary down-regulator luteinising hormone-releasing hormone (LHRH) agonist is given as an injection, either monthly or quarterly (goserelin and triptorelin). This stops the making of testosterone in the testes and the production of luteinising hormone Hilary Baker

Lead Uro-oncology CNS, University College London Hospitals, NHS Foundations Trust

S14

(LH) from the pituitary, causing a chemical castration. Other drugs called anti-androgens (bicalutamide and cyproterone acetate) prevent testosterone affecting the cancer cells. They are given as a tablet 2 weeks before the first LHRH injection to prevent a ‘testosterone flare’, which can occur after the first dose of treatment as the pituitary gland secretes extra LH before blocking testosterone release (Nelius and Filleur, 2009). Bicalutamide is prescribed for younger men to help preserve their potency; however, they can develop gynaecomastia (enlargment of breast tissue), which is managed with anti-oestrogens and prophylactic radiotherapy (EAU, 2014). ADT can be given in several ways to manage PC, including as a monotherapy for some elderly men who have comorbidities and are not suitable for more radical treatments. Monotherapy is also given to men who, on initial diagnosis, have metastatic disease and for men who have had standard primary treatment and then develop recurrence of the disease. This is called a biochemical recurrence and prescribing ADT will not be curative, but will manage the PC (EAU, 2014). Other patients with localised PC and intermediate risk of recurrence will have neoadjuvant therapy before and following radiation treatment. Evidence has shown that combined treatment improves men’s survival rate (Bolla et al, 1997). Some patients will have adjuvant therapy if they are at risk of recurrence after their primary treatment depending on their Gleason score, extent of the tumour, and lymph node involvement. Evidence has shown patients who have ADT after primary treatment live longer (Kumar et al, 2006). ADT has side effects that can affect the patient’s quality of life. Healthcare professionals (HCPs) will support patients and their partners through this treatment (National Institute for Health and Care Excellence (NICE), 2014). A common side effect is hot flushes, which can be mild to severe, occurring because of hormone-level changes. Patients are advised to wear cotton clothing, keep in a cool environment, cut out eating spicy foods, and reduce intake of caffeine and alcohol. Medroxyprogesterone (20 mg per day) can be prescribed to manage the side effects. Complementary therapies have been proven to provide no relief (NICE, 2014). The reduction of androgens causes

patients to experience sexual dysfunction and loss of libido. This can be distressing for patients and their partners. HCPs must ensure patients are fully informed and supported with early and ongoing interventions, and referred for psychosexual support as needed (NICE, 2014). Patients are at risk of developing cardiometabolic symptoms, of putting on weight and losing muscle mass, putting them at risk of cardiovascular disease and diabetes. Evidence shows that weight control and resistance exercise help maintain muscle strength (Collins et al, 2012). Fatigue, osteoporosis, and low mood are often experienced on ADT. Men are advised to eat a healthy diet, take regular exercise, and seek advice from their HCP if side effects become symptomatic (Prostate Cancer UK, 2012). Some men who initially respond to LHRH agonists will eventually become hormone resistant; this is detected by a rising PSA (National Cancer Institute, 2014). Subsequently, patients are prescribed maximum androgen blockade (MAB) (LHRH and an anti-androgen medication). At this time the prognosis is poor, although they patient may be asymptomatic. Care should be managed with therapy to prolong quality of life. Various treatments are being developed for castration-resistant PC (CRPC), including trials where patients with a good performance status (Sørensen et al, 1993) are encouraged to participate. Patients enquiring about trials should discuss them with their HCP and obtain further details from Cancer Research UK. Oestrogen therapy, diethylstilbestrol 1 mg and 75 mg aspirin daily, can be prescribed in selected CRPC patients who have good performance status; however the treatment can cause cardiotoxicity and blood clots (EAU, 2014). Degarelix is a new LHRH antagonist, licensed in the UK for advanced prostate cancer, but is not approved by NICE (2014) and therefore not available on the NHS. The drug is initially given with a loading dose followed by monthly injections into the abdomen and stops the immediate production of LH in the pituitary. Evidence shows the drug manages CRPC with no testosterone flare and minimal hormone therapy-related side effects (Carter and Keam, 2014). Docetaxel and cabazitaxel are chemotherapy drugs that destroy cells and are used as a second- line treatment for CRPC. Docetaxel is infused over an hour once weekly, for 10 cycles,

© 2014 MA Healthcare Ltd

Choosing a prostate cancer drug

British Journal of Nursing, 2014 (Oncology Supplement), Vol 23, No 16

British Journal of Nursing. Downloaded from magonlinelibrary.com by 165.123.034.086 on November 28, 2015. For personal use only. No other uses without permission. . All rights reserved.

PRESCRIBING INFORMATION ZYTIGA®▼ 250mg Tablets ACTIVE INGREDIENT(S): Abiraterone acetate Please refer to Summary of Product Characteristics (SmPC) before prescribing. INDICATION(S): Taken with prednisone or prednisolone for the treatment of metastatic castration resistant prostate cancer in adult men who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated. The treatment of metastatic castration resistant prostate cancer in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen. DOSAGE & ADMINISTRATION: Adults: 1000 mg (4 tablets) single daily dose. Not with food as this increases the systemic exposure (take dose at least two hours after eating; no food for at least one hour postdose). Swallow whole with water. Take with recommended dose of prednisone or prednisolone of 10 mg daily. Medical castration with LHRH analogue should be continued during treatment in patients not surgically castrated. Children: No relevant use. Hypokalaemia: In patients with pre-existing, or who develop hypokalaemia during treatment with Zytiga, consider maintaining potassium level at ≥4.0 mM. Patients who develop Grade ≥ 3 toxicities (hypertension, hypokalaemia, oedema and other nonmineralocorticoid toxicities) stop treatment and start appropriate medical management. Do not restart Zytiga until symptoms of the toxicity have resolved to Grade 1 or baseline. Renal impairment: No dose adjustment, however no experience in patients with prostate cancer and severe renal impairment; caution advised. Hepatotoxicity: If hepatotoxicity develops (ALT or AST >5x upper limit of normal ULN), stop treatment immediately until liver function returns to baseline; restart Zytiga at 500 mg (2 tablets) once daily and monitor serum transaminases at least every 2 weeks for 3 months and monthly thereafter (see Special warnings & precautions). If hepatotoxicity recurs on reduced dose, stop treatment. If severe hepatotoxicity develops (ALT or AST 20xULN), discontinue Zytiga and do not restart. Hepatic impairment: Mild (Child-Pugh class A) - no dose adjustment required. Moderate (Child-Pugh class B) - approximately 4x increased systemic exposure after single oral doses of 1,000 mg. Moderate/ Severe (Child-Pugh class B or C) – no clinical data for multiple doses. Use with caution in moderate impairment, benefit should clearly outweigh risk. CONTRAINDICATIONS: Pregnancy or potential to be pregnant. Hypersensitivity to active substance or any excipients. Severe hepatic impairment (Child-Pugh Class C). SPECIAL WARNINGS & PRECAUTIONS: Zytiga may cause hypertension, hypokalaemia and fluid retention due to increased mineralocorticoid levels.Cardiovascular: Caution in patients with history of cardiovascular disease. In patients with a significant risk for congestive heart failure (history of cardiac failure, uncontrolled hypertension, ischaemic heart disease) consider an assessment of cardiac function before treating (echocardiogram). Safety not established in patients with left ventricular ejection fraction < 50% or NYHA Class II to IV (pre-chemotherapy) and III or IV (postchemotherapy) heart failure. Before treatment cardiac failure should be treated and cardiac function optimised. Correct and control Hypertension, hypokalaemia and fluid retention pre-treatment. Caution in patients whose medical conditions might be compromised by hypertension, hypokalaemia or fluid retention e.g. heart failure, severe or unstable angina pectoris, recent myocardial infarction or ventricular arrhythmia, severe renal impairment. Monitor blood pressure, serum potassium and fluid retention and other signs and symptoms of congestive heart failure before treatment, then every two weeks for 3 months, and monthly thereafter. Consider discontinuation if there is a clinically significant decrease in cardiac function. Hepatotoxicity & Hepatic impairment: Measure serum transaminases pre-treatment and every two weeks for first three months, then monthly. If symptoms/signs suggest hepatotoxicity, immediately measure serum transaminases. If ALT or AST > 5x ULN, stop treatment and monitor liver function. Restart treatment after liver function returns to baseline; use reduced dose (see dosage and administration). No clinical data in patients with active or symptomatic viral hepatitis. Corticosteroid withdrawal: Monitor for adrenocortical insufficiency if prednisone or prednisolone is withdrawn. Monitor for mineralocorticoid excess if Zytiga continued after corticosteroids withdrawn. Bone density: Decreased bone density may be accentuated by Zytiga plus glucocorticoid. Prior use of ketoconazole: Lower response rates may occur in patients previously treated with ketoconazole for prostate cancer. Hyperglycaemia: Use of glucocorticoids could increase hyperglycaemia, measure blood sugar frequently in patients with diabetes. Use with chemotherapy: Safety and efficacy of concomitant use of Zytiga with cytotoxic chemotherapy not established. Intolerance to excipients: Not to be taken by patients with galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Take sodium content into account for those on controlled sodium diet. Potential risks: Anaemia and sexual dysfunction may occur in men with metastatic castration resistant prostate cancer including those taking Zytiga. Skeletal Muscle Effects: Cases of myopathy reported. Some patients had rhabdomyolysis with renal failure. Caution is recommended in patients concomitantly treated with drugs known to be associated with myopathy/rhabdomyolysis. SIDE EFFECTS: Very common: urinary tract infection, hypokalaemia, hypertension, diarrhoea, peripheral oedema. Common: sepsis, hypertriglyceridaemia, cardiac failure (including congestive heart failure, left ventricular dysfunction and decreased ejection fraction), angina pectoris, arrhythmia, atrial fibrillation, tachycardia, dyspepsia, increased alanine aminotransferase, increased aspartate aminotransferase, rash, haematuria, fractures (includes all fractures with the exception of pathological fracture). Other side effects: adrenal insufficiency, myopathy, rhabdomyolysis. Refer to SmPC for other side effects. FERTILITY/ PREGNANCY/LACTATION: Not for use in women. Not known whether abiraterone or its metabolites are present in semen. A condom is required if the patient is engaged in sexual activity with a pregnant woman. If the patient is engaged in sexual activity with a woman of childbearing potential, a condom is required along with another effective contraceptive method. Studies have shown that abiraterone affected fertility in male and female rats, but these effects were fully reversible. INTERACTIONS: Caution with drugs activated by or metabolised by CYP2D6 particularly when there is a narrow therapeutic index e.g. metoprolol, propranolol, desipramine, venlafaxine, haloperidol, risperidone, propafenone, flecanide, codeine, oxycodone and tramadol. Avoid strong inducers of CYP3A4 (e.g. phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine, phenobarbital, St John’s wort). Zytiga is a CYP2C8 inhibitor (in vitro data). Examples of medicinal products metabolised by CYP2C8 incl paclitaxel, repaglinide. No clinical data are available on the use of Zytiga with CYP2C8 substrates. May increase concentrations of drugs eliminated by OATP1B1. Food (see Dosage & Administration). Refer to SmPC for full details of interactions. LEGAL CATEGORY: POM PRESENTATIONS, PACK SIZES, MARKETING AUTHORISATION NUMBERS & BASIC NHS COSTS EU/1/11/714/001; 120 tablets: £2930. MARKETING AUTHORISATION HOLDER: JANSSEN-CILAG INTERNATIONAL NV, Turnhoutseweg 30, B-2340 Beerse, Belgium. FURTHER INFORMATION IS AVAILABLE FROM: Janssen-Cilag Ltd, 50100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG, UK. © Janssen-Cilag Ltd 2014

with dexamethasone, but is stopped with evidence-supported progression of PC. Cabazitaxel is licensed for use in the UK, but is not yet widely available on the NHS. Abiraterone is licensed for patients post- docetaxel chemotherapy where the disease has stopped responding to the treatment. Abiraterone is given as a daily tablet taken with prednisolone and prescribed until either disease progression, the patient experiences intolerable side effects, or withdrawal from treatment. Side effects are few, but can include liver problems, fluid retention and hypertension, which should be monitored. The drug is not available on the NHS in England if the patient has had enzalutamide. However, the side effect profile is tolerable and there is an overall survival benefit of 3 months, delaying the time for palliative care symptom management (Payne and Mason, 2011). Enzalutamide is an oral, daily androgen inhibitor, and is also recommended for men with metastatic CRPC, who have progressed during or after docetaxel and not previously been treated with abiraterone. Side effects are minimal; the most common reported are hot flushes and fatigue. Enzalutamide should be available on the NHS this October (NICE, 2014b). Dexametasone is a third-line hormonal therapy for CRPC shown to improve progression-free survival and pain management (Venkitaraman et al, 2008). PC has many pharmacological options and it is essential to discuss these with patients to ensure they are fully aware of their disease, the effects of treatment, and how to manage them. HCPs need to ensure that care provided is patient-centred and BJN holistic throughout the patient’s journey. American Joint Committee on Cancer (2009) Prostate Cancer Staging. 7th edn. http://tinyurl.com/lewlnvs (accessed 20 August 2014) Bolla M, Gonzalez D, Warde P et al (1997) Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med 337(5): 295-300. Cancer Research UK (2014) Prostate Cancer Statistics Key Facts. http://tinyurl.com/ otnsjpm (accessed 20 August 2014) Carter NJ, Keam SJ (2014) Degarelix: a review of its use in patients with prostate cancer. Drugs 74(6):699-712 doi: 10.1007/s40265-014-0211-y Collins L, Mohammed N, Ahmad T, Basaria S (2012) Androgen deprivation therapy for prostate cancer: implications for cardiometabolic clinical care. J Endocrinol Invest 35(3): 332-9. doi: 10.3275/8284 European Association of Urology (2014) Guidelines on Prostate Cancer. http:// tinyurl.com/oc4uevn (accessed 20 August 2014) Kumar S, Shelley M, Harrison C, Coles B, Wilt TJ, Mason MD (2006) Neo-adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer. Cochrane Database Syst Rev 18(4) CD006019 National Cancer Institute (2014) Fact sheet. http://tinyurl.com/lgzcsol (accessed 20 August 2014) Nelius T, Filleur S (2009) PSA surge/flare-up in patients with castration-refractory prostate cancer during the initial phase of chemotherapy. Prostate 69(16):1802-7. doi: 10.1002/pros.21024 National Institute for Health and Care Excellence (2014a) Prostate cancer: diagnosis and treatment. http://tinyurl.com/pxdo5mh (accessed 20 August 2014) National Institute for Health and Care Excellence (2014b) Enzalutamide for metastatic hormone-relapsed prostate cancer previously treated with a docetaxel-containing regimen. http://tinyurl.com/kwl3c5d (accessed 20 August 2014) Payne H, Mason M (2011) Androgen deprivation therapy as adjuvant/neoadjuvant to radiotherapy for high-risk localised and locally advanced prostate cancer: recent developments. Br J Cancer 105(11):1628-34 doi: 10.1038/bjc.2011.385 Phillips I, Shah SI, Duong T, Abel P, Langley RE (2014) Androgen deprivation therapy and the re-emergence of parenteral estrogen in prostate cancer. Oncol Hematol Rev 10(1): 42-7 Prostate Cancer UK (2012) Healthy living. http://tinyurl.com/kbhdlcc (accessed 28 August 2014) Prostate Cancer UK (2012) External Beam Radiotherapy http://tinyurl.com/os8lxn2 (accessed 28 August 2014) Sørensen JB, Klee M, Palshof T, Hansen HH (1993) Performance status assessment in cancer patients. An inter-observer variability study. Br J Cancer 67(4):773-5 Venkitaraman R, Thomas K, Huddart RA, Horwich A, Dearnaley DP, Parker CC (2008) Efficacy of low-dose dexamethasone in castration-refractory prostate cancer. BJU Int 101(4): 440-3

Prescribing information last revised: May 2014

© 2014 MA Healthcare Ltd

This medicinal product is subject to additional monitoring and it is therefore important to report any suspected adverse reactions related to this medicinal product. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov. uk/yellowcard. Adverse events should also be reported to Janssen-Cilag Ltd on 01494 567447.

©Janssen-Cilag Ltd. PHGB/ZYT/1213/0006(2)a Date of Preparation: July 2014



British Journal of Nursing, 2014 (Oncology Supplement), Vol 23, No 16

British Journal of Nursing. Downloaded from magonlinelibrary.com by 165.123.034.086 on November 28, 2015. For personal use only. No other uses without permission. . All rights reserved.

Choosing a prostate cancer drug.

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