Drug reference
Prophylaxis and treatment of acute hyperuricaemia, before and during initiation of chemotherapy, in patients with haematological malignancy and high tumour burden at risk of rapid lysis ▶BY INTRAVENOUS INFUSION ▶Adult: 200 micrograms/kg once daily for up to 7 days according to plasma-uric acid concentration
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G6PD deficiency
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Atopic allergies
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▶Common or very common Diarrhoea. fever. headache. nausea. skin reactions. vomiting ▶Uncommon Bronchospasm. haemolysis. haemolytic anaemia. hypersensitivity. hypotension. methaemoglobinaemia. seizure ▶Rare or very rare Rhinitis ▶Frequency not known Muscle contractions involuntary
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Manufacturer advises avoid—no information available.
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Manufacturer advises avoid—no information available.
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Monitor closely for hypersensitivity. l EFFECT ON LABORATORY TESTS May interfere with test for uric acid—consult product literature.
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For intravenous infusion (Fasturtec ®), give intermittently in Sodium chloride 0.9%; reconstitute with solvent provided; gently swirl vial without shaking to dissolve; dilute requisite dose to 50 mL with infusion fluid and give over 30 minutes.
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There can be variation in the licensing of different medicines containing the same drug. Powder and solvent for solution for infusion ▶Fasturtec (Sanofi) Rasburicase 1.5 mg Fasturtec 1.5mg powder and solvent for solution for infusion vials | 3 vial P £208.39 (Hospital only) Rasburicase 7.5 mg Fasturtec 7.5mg powder and solvent for solution for infusion vials | 1 vial P £347.32 (Hospital only) Hormone responsive malignancy Immune system and malignant disease Breast cancer Description of condition Breast cancer is the most common form of malignancy in women, especially in those aged over 50 years. Established risk factors include age, early onset of menstruation, late menopause, older age at first completed pregnancy, and a family history of breast cancer. The use of oral contraceptives or hormone replacement therapy (HRT) is also associated with an increased risk of breast cancer. Breast cancer in men is rare. Although risk factors are not fully understood, it may be associated with abnormalities of sex hormone metabolism, including those caused by liver disease or testicular trauma, genetic predisposition, and environmental risk factors such as industrial exposure to chronic heat. Additional risk factors include obesity and alcohol consumption. Physical activity and breast-feeding protect against breast cancer. Non-invasive breast cancer, also known as ductal carcinoma in situ, is when the cancer remains localised in the ducts. However, in most cases, the cancer is invasive at the time of diagnosis, which means that malignant cells are liable to spread beyond the immediate area of the tumour. Invasive breast cancer, where malignant cells spread beyond the ducts, can be defined as early breast cancer (stage I/II), locally advanced disease (stage III) and advanced disease (stage IV). Aims of treatment Reducing mortality, increasing progression-free and disease- free survival and improving quality of life are the main aims of treatment, and are dependent on the stage of the disease. Surgery and radiotherapy aim to remove the tumour mass, whilst adjuvant drug therapy (drug treatment following surgery) aims to reduce the risk of disease recurrence and the risk of developing invasive disease. Neoadjuvant drug therapy (drug treatment before surgery) aims to reduce the size of the tumour to allow breast-conserving surgery to be possible and to reduce axillary lymph node involvement. Advanced breast cancer is not curable, and treatment aims to prolong survival, relieve symptoms and improve quality of life. Overview The management of patients with breast cancer involves surgery, radiotherapy, drug therapy, or a combination of these. The course of the disease and the therapeutic approach vary depending on the characteristics of the cancer. Factors such as patient age, menopausal status, tumour size and grade, involvement of axillary lymph nodes or skin, and the presence of hormone receptors within the tumour, may inform the extent and aggressiveness of the disease. g The risks and benefits of each therapy should be discussed with the patient before being started. h Early and locally advanced breast cancer For operable breast cancer, treatment involves surgery to the breast (breast-conserving surgery or mastectomy) and to the axillary lymph nodes, with or without radiotherapy to reduce local recurrence rates. This is often followed by adjuvant drug therapy to eradicate the micro-metastases that cause relapses. g In women with invasive breast cancer, radiotherapy is recommended after breast-conserving surgery with clear margins (no cancer cells are found at the edges of the removed tissue), as it reduces local recurrence rates. However, the use of radiotherapy may be omitted if risk of local recurrence is very low and the woman is willing to take adjuvant endocrine therapy for a minimum of 5 years. Radiotherapy is also recommended after mastectomy in patients with node-positive invasive breast cancer or involved resection margins (cancer cells are found at the edges of the removed tissue). It should also be considered in patients with node-negative T3 or T4 invasive breast cancer. h Adjuvant drug therapy Adjuvant drug therapy may include the use of chemotherapy, endocrine therapy, biological therapy, or bisphosphonate therapy. g The decision to use adjuvant drug therapy should be based on the risks and benefits of treatment, disease prognosis and predictive factors such as oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor 2 (HER2) status of the primary tumour. In women with invasive breast cancer in only one breast who have not received treatment, including the use of neoadjuvant chemotherapy, NICE clinical guideline 101 recommends the use of the PREDICT tool to estimate prognosis and the absolute benefits of adjuvant therapy (www.predict.nhs.uk). h Chemotherapy g Adjuvant anthracycline–taxane combination chemotherapy is recommended in patients with invasive breast cancer who are at sufficient risk of disease recurrence to require chemotherapy. h The choice of chemotherapy regimen is usually guided by local policy, Cancer Alliances, and the National Cancer Drugs Fund list. Biological therapy g Trastuzumab p. 935 should be offered to patients with tumour size T1c and above HER2-positive invasive breast cancer, in combination with surgery, chemotherapy, or radiotherapy. It should also be considered in patients with a smaller tumour size (T1a or T1b) depending on their co- morbidities, prognosis, and possible toxicity with concomitant chemotherapy. Cardiac function should be regularly assessed in patients receiving trastuzumab p. 935, and particular caution should be taken in patients with underlying cardiac disease (consult product literature for further details). h Endocrine therapy g Tamoxifen p. 1005 should be used as initial adjuvant endocrine therapy in men and premenopausal women with oestrogen-receptor-positive invasive breast cancer. In addition, ovarian function suppression with a gonadotropin- releasing hormone (GnRH) should be considered in premenopausal women, taking into account the risk of temporary menopause. h Ovarian function suppression aims to stop the production of circulating oestrogen, which can stimulate breast cancer progression. It may be most beneficial in women who are at sufficient risk of disease recurrence to have been offered chemotherapy. g In postmenopausal women with oestrogen-receptor positive invasive breast cancer who are at medium or high- risk of disease recurrence, an aromatase inhibitor should be given as first-line therapy. Alternatively, tamoxifen should be given if an aromatase inhibitor is not tolerated or is contra-indicated, or if the risk of disease recurrence is low. h Extended endocrine therapy g Extended endocrine therapy (total duration longer than 5 years) with an aromatase inhibitor [unlicensed indication] should be offered to postmenopausal women with oestrogen-receptor-positive invasive breast cancer at medium or high-risk of disease recurrence who have been taking tamoxifen for 2 to 5 years. Extended therapy should also be considered in postmenopausal women at low risk of disease recurrence. Extended tamoxifen therapy for longer than 5 years can also be considered in both premenopausal and postmenopausal women with oestrogen-receptor-positive invasive breast cancer. h Endocrine therapy for ductal carcinoma in situ g Following breast-conserving surgery, endocrine therapy should be offered to women with oestrogen-positive ductal carcinoma in situ, if radiotherapy is recommended but not given. If radiotherapy is not recommended, the use of endocrine therapy should also be considered. h Bisphosphonate therapy Zoledronic acid p. 771 and sodium clodronate p. 770 have been shown to improve disease-free survival and overall survival in postmenopausal women with node-positive invasive breast cancer. However, there is insufficient evidence to recommend their use in premenopausal women. g Intravenous zoledronic acid [unlicensed indication] or oral sodium clodronate [unlicensed indication] should be offered to postmenopausal women with lymph-node- positive invasive breast cancer. Treatment should be considered in those with lymph-node-negative invasive breast cancer who are at high-risk of recurrence. Bisphosphonate therapy is also recommended in women at high-risk of osteoporosis due to the use of aromatase inhibitors in postmenopausal women, or in women with treatment-induced premature menopause. For further information, see Guidance for the management of breast cancer treatment-induced bone loss: a consensus position statement from a UK expert group, 2008. h Neoadjuvant drug therapy Neoadjuvant drug therapy may involve the use of chemotherapy or endocrine therapy. Chemotherapy g Neoadjuvant chemotherapy should be offered to reduce tumour size in patients with oestrogen-receptor-negative invasive breast cancer. In patients with oestrogen-receptor- positive invasive breast cancer, chemotherapy should be considered. In patients with HER2-positive invasive breast cancer, neoadjuvant chemotherapy should be offered in combination with trastuzumab p. 935 and pertuzumab p. 930. A chemotherapy regimen containing both a platinum [unlicensed indication] and an anthracycline should be considered in patients with triple-negative invasive breast cancer (oestrogen-receptor-negative, progesterone-receptor negative and HER2-negative). h Endocrine therapy g If chemotherapy is not indicated, neoadjuvant endocrine therapy should be considered as an alternative in postmenopausal women with oestrogen-receptor-positive invasive breast cancer. h Chemotherapy and endocrine therapy are equally effective in postmenopausal women in terms of breast-conservation and shrinking of the tumour. Although chemotherapy is more effective than endocrine therapy at shrinking the tumour in premenopausal women, some tumours may respond to endocrine treatment. Advanced breast cancer Treatment of advanced breast cancer depends on the patient’s treatment history, disease severity, and oestrogen receptor and HER2 status. Endocrine therapy g For the majority of patients with oestrogen-receptor- positive advanced breast cancer, endocrine therapy is recommended as first-line treatment. Aromatase inhibitors should be offered to postmenopausal women with no previous history of endocrine treatment, or to those previously treated with tamoxifen p. 1005. Tamoxifen in combination with ovarian function Immune system and malignant disease suppression should be offered as first-line treatment to pre- and perimenopausal women with oestrogen-receptor- positive advanced breast cancer not previously treated with tamoxifen. Ovarian function suppression should be offered to pre- and perimenopausal women who have had disease progression despite treatment with tamoxifen. Tamoxifen should be offered as first-line treatment to men with oestrogen-receptor-positive advanced breast cancer. h Chemotherapy g Chemotherapy should be offered as first-line treatment in patients with oestrogen-receptor-positive advanced breast cancer that is imminently life-threatening or requires early relief of symptoms because of significant visceral organ involvement. Once chemotherapy treatment is completed, endocrine therapy should be offered. h The choice of chemotherapy regimen is usually guided by local policy, Cancer Alliances, and the National Cancer Drugs Fund list. Biological therapy g Trastuzumab is recommended for the treatment of HER2-positive advanced breast cancer. It is used in combination with paclitaxel p. 976 in those who have not received chemotherapy for metastatic breast cancer, and as monotherapy for patients who have received at least two chemotherapy regimens for metastatic breast cancer (see trastuzumab National funding/access decisions). h Bisphosphonate therapy g The use of bisphosphonates should be considered in patients with metastatic breast cancer to reduce pain and prevent skeletal complications of bone metastases. h Familial breast cancer g Chemoprevention should be offered to all women who have been identified as being at high-risk of developing breast cancer. Chemoprevention should also be considered in women at moderate-risk. Other strategies to reduce breast cancer risk should also be considered, for example bilateral mastectomy or bilateral oophorectomy. Women who were at high-risk of breast cancer and have undergone a bilateral mastectomy should not receive chemoprevention. h Treatment options for chemoprevention g Chemoprevention should only be continued for 5 years. Tamoxifen is recommended for premenopausal women who do not have a history of, or increased risk of thromboembolic disease or endometrial cancer. Anastrozole p. 1006 [unlicensed indication] is recommended in postmenopausal women who do not have severe osteoporosis, see Osteoporosis p. 764. In women who have severe osteoporosis, or who do not wish to take anastrozole, treatment with tamoxifen can be given, provided there is no history, or increased risk of thromboembolic disease or endometrial cancer. Alternatively, raloxifene hydrochloride p. 796 is an option [unlicensed indication] in postmenopausal women with a uterus who do not wish to take tamoxifen, unless there is a history or increased risk of thromboembolic disease. h Treatment of menopausal symptoms g Some treatments used in the management of breast cancer, such as tamoxifen or ovarian function suppression may lead to menopausal symptoms or early menopause, and women should be counselled about these side-effects prior to starting any of these treatments. Women diagnosed with breast cancer should discontinue their hormone replacement therapy (HRT) because of possible tumour stimulation and interference with adjuvant endocrine therapy. HRT should not be offered routinely to women with menopausal symptoms if they have a history of breast cancer; however, in exceptional circumstances, HRT Immune system and malignant disease can be offered to women with severe menopausal symptoms once the associated risks have been discussed. Selective serotonin re-uptake inhibitor (SSRIs) antidepressants may be offered to relieve menopausal symptoms such as hot flushes in women with breast cancer who are not taking tamoxifen. h Clonidine hydrochloride p. 156, venlafaxine p. 386 [unlicensed indication] and gabapentin p. 331 [unlicensed indication] are sometimes used for the treatment of hot flushes in women with breast cancer after discussion with the patient and information given about side effects. Useful Resources Early and locally advanced breast cancer: diagnosis and management. National Institute for Health and Care Excellence. Clinical guideline 101. July 2018. www.nice.org.uk/guidance/ng101 Advanced breast cancer: diagnosis and treatment. National Institute for Health and Care Excellence. Clinical guideline 81. August 2017. www.nice.org.uk/guidance/cg81 Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer. National Institute for Health and Care Excellence. Clinical guideline 164. June 2013 (updated March 2017). www.nice.org.uk/guidance/cg164 Guidance for the management of breast cancer treatment- induced bone loss: a consensus position statement from a UK expert group, 2008. nos.org.uk/media/98027/bone-health-guidelines-breast-cancer- treatments.pdf Patient decision aids: Taking a medicine to reduce the chance of developing breast cancer: postmenopausal women at moderately increased risk; Taking a medicine to reduce the chance of developing breast cancer: postmenopausal women at high risk. National Institute for Health and Care Excellence. March 2017. www.nice.org.uk/about/what-we-do/our-programmes/nice- guidance/nice-guidelines/shared-decision-making Prostate Cancer Description of condition Prostate cancer is the most common form of cancer affecting men. It can also affect transgender women, as the prostate is usually conserved after gender-confirming surgery. The main risk factors are age (most cases being diagnosed in men over 70 years of age), ethnicity (more common in black African-Caribbean men), obesity, and a familial component. Prostate cancer is usually slow-growing and asymptomatic at diagnosis, however, the presenting symptoms of advanced disease are usually urinary outflow obstruction, or, pelvic or back pain due to bone metastases. Treatment decisions are guided by baseline prostate specific antigen (PSA) levels, tumour grade (Gleason score), the stage of the tumour, the patient’s life expectancy (based on age and comorbid conditions), treatment morbidity, and patient preference. Aims of treatment Reducing mortality, increasing progression-free and disease- free survival and improving quality of life are the main aims of treatment, and are dependent on the stage of disease. Watchful waiting or active surveillance aim to monitor for disease progression, while radical treatments such as prostatectomy and radiotherapy aim to eliminate the malignancy. Hormone therapy and chemotherapy aim to slow the progression of prostate cancer and to control symptoms. In metastatic disease, treatment is aimed at prolonging survival and relieving symptoms. Overview g Treatment options for patients with prostate cancer include watchful waiting, active surveillance, prostatectomy, radiotherapy (such as external beam), brachytherapy, hormone therapy, and chemotherapy. The benefits and risks of each option should be discussed with patients. h Watchful waiting is a strategy for ’controlling’ rather than ’curing’ prostate cancer and is aimed at patients in whom curative treatment is unsuitable or declined. It involves monitoring for disease progression and is often suitable in patients not likely to suffer significant morbidity from their prostate cancer. Active surveillance, a ’curative’ strategy, is aimed at patients who do not wish to have immediate treatment. It involves the deferred use of radical treatment until disease progression occurs or until the patient requests treatment. For information on monitoring in watchful waiting or the protocol for active surveillance, see NICE clinical guideline Prostate Cancer (see Useful resources). g At any stage of care, when moving from active surveillance to radical treatment, patient preferences, comorbidities and life expectancy should be taken into account. h Hormone therapy includes anti-androgen therapy—to block the effects of androgens, androgen deprivation therapy such as a luteinising hormone-releasing hormone (LHRH) agonist, or a gonadorelin antagonist—to reduce androgen levels, and bilateral orchidectomy—to remove the endogenous supply of androgens. In patients with localised prostate cancer, the choice of treatment is guided by whether the disease is considered low, intermediate, or high risk according to the Gleason score, the serum PSA level, and the tumour clinical stage. High risk localised prostate cancer is also included in the definition of locally advanced prostate cancer. For further information on risk stratification, see NICE clinical guideline Prostate cancer (see Useful resources). Localised or locally advanced prostate cancer g In patients with low-risk localised prostate cancer, offer a choice between active surveillance, radical prostatectomy or radiotherapy. Radical treatment should be offered to patients with localised prostate cancer undergoing active surveillance who show evidence of disease progression. In patients with intermediate-risk localised prostate cancer, radical treatments (prostatectomy or radiotherapy) should be offered, and for those who decline them, active surveillance can be considered. In patients with high-risk localised prostate cancer (when there is a realistic prospect of long-term disease control), and in those with locally advanced disease, radical prostatectomy or radiotherapy should be offered. In patients with intermediate-risk and high-risk localised prostate cancer who have chosen radical radiotherapy, this should be offered in combination with androgen deprivation therapy. Androgen deprivation therapy should be given for 6 months before, during or after radiotherapy; in patients with high-risk localised prostate cancer, consider continuing therapy for up to 3 years. Brachytherapy in combination with radiotherapy can also be considered in these patients. In patients with newly diagnosed non-metastatic prostate cancer discuss the option of chemotherapy with docetaxel p. 975 [unlicensed indication] if they are starting long term androgen deprivation therapy, have no significant co-morbidities and have high-risk disease. Pelvic radiotherapy should be considered in those with locally advanced prostate cancer who have a higher than 15% risk of pelvic lymph node involvement and are to receive neoadjuvant hormonal therapy and radical radiotherapy. h Metastatic prostate cancer g Patients with newly diagnosed metastatic prostate cancer who do not have significant comorbidities, should be offered chemotherapy with docetaxel. Bilateral orchidectomy should be offered to all patients with metastatic prostate cancer as an alternative to continuous LHRH agonist treatment. Anti-androgen monotherapy with bicalutamide p. 999 [unlicensed indication] can be offered to those who are willing to accept the adverse impact on overall survival and gynaecomastia, in the hope of retaining sexual function. However, if satisfactory sexual function is not maintained, stop bicalutamide and start androgen deprivation therapy. Abiraterone acetate below (in combination with prednisone or prednisolone p. 716) and enzalutamide p. 999 are both recommended as options for the treatment of hormone-relapsed metastatic prostate cancer in patients who have no or mild symptoms after androgen deprivation therapy has failed, and before chemotherapy is indicated. In patients with hormone-relapsed metastatic prostate cancer, chemotherapy with docetaxel can be used. It is recommended that treatment with docetaxel is stopped after 10 cycles, or if severe adverse events occur, or if there is evidence of disease progression. Abiraterone acetate (in combination with prednisone or prednisolone) and enzalutamide are also recommended in hormone-relapsed metastatic prostate cancer if disease has progressed during or after treatment with a docetaxel- containing chemotherapy regimen. In patients with hormone-relapsed metastatic prostate cancer, a corticosteroid such as dexamethasone p. 712 can be offered as third line therapy after androgen deprivation therapy and anti-androgen therapy. In patients with hormone-relapsed metastatic prostate cancer, zoledronic acid p. 771 can be considered to prevent or reduce skeletal-related events. Bisphosphonates can be considered for pain relief in hormone-relapsed metastatic prostate cancer when other treatments have failed to give satisfactory pain relief. h Management of side-effects of treatment g Patients should be informed about the side-effects of treatment; particularly urinary and sexual dysfunction, loss of fertility, radiation-induced enteropathy, osteoporosis, gynaecomastia, fatigue, and hot flushes. h Tumour flare due to an initial surge in testosterone concentrations has been reported in the initial stages of treatment with LHRH agonists; the manufacturers advise that the use of prophylactic anti-androgen therapy (such as cyproterone acetate p. 812) should be considered. g Although there is limited evidence, intermittent therapy may be considered for patients who are having long- term androgen deprivation therapy to reduce side-effects. Patients who are on androgen deprivation therapy should be offered a supervised exercise program (at least twice a week for 12 weeks) to reduce fatigue and improve quality of life. Medroxyprogesterone acetate p. 856 [unlicensed indication] can be used, initially for up to 10 weeks, to manage troublesome hot flushes caused by long-term androgen suppression; cyproterone acetate can be considered as an alternative if medroxyprogesterone acetate is not effective or not tolerated. Patients who experience loss of sexual function should have access to specialist erectile dysfunction services and be considered for treatment with a phosphodiesterase type-5 inhibitor. A bisphosphonate should be offered to patients who have osteoporosis and who are having androgen deprivation therapy; denosumab p. 774 is an alternative if bisphosphonates are not appropriate. Gynaecomastia can occur with long-term (longer than 6 months) bicalutamide p. 999 treatment. Prophylactic radiotherapy (within the first month of treatment) should be Immune system and malignant disease offered; or if radiotherapy is unsuccessful, weekly tamoxifen p. 1005 [unlicensed indication] can be considered. h Useful Resources Prostate cancer: diagnosis and management. National Institute for Health and Care Excellence. NICE guideline 131. May 2019. www.nice.org.uk/guidance/ng131 Other drugs used for Hormone responsive malignancy Buserelin, p. 778. Ethinylestradiol, p. 802. Goserelin, p. 779. Leuprorelin acetate, p. 780. Norethisterone, p. 806. Triptorelin, p. 781 ANTINEOPLASTIC DRUGS › ANTI-ANDROGENS
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200 micrograms/kg once daily for up to 7 days
First-line fragment. Read the complete Indications and Dose section above.
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