Bicalutamide (Casodex) For the treatment of prostate cancer
Committee’s Verdict: RESTRICTED USE BNF: 8.3.4.2 Bicalutamide 150mg: The decision to use bicalutamide 150mg should be taken by the specialist. It is then appropriate for GPs to prescribe and monitor treatment over the long term with the guidance of an effective shared care agreement. Bicalutamide 50mg: The licensed indications for bicalutamide 50mg are limited (see below). Initiation should be the responsibility of the specialist. Once the patient’s condition is stabilised, it is then appropriate for GPs to prescribe and monitor treatment over the long term, with the guidance of an ESCA. 27/07/2012: Current MTRAC opinion is that this drug should continue to be initiated by a specialist but that no ESCA is required, provided that the initiating specialist specifies who has the responsibility for monitoring LFTs and PSA.
Licensed Indication Safety
Bicalutamide 150mg:* Across the studies the most common adverse events ‘In patients with locally advanced prostate cancer (T3- with bicalutamide were gynaecomastia and breast pain. T4, any N, M0; T1-T2, N+, M0),’ bicalutamide 150mg ‘is Hepatic changes (elevated transaminase levels, indicated as immediate therapy either alone or as cholestasis and jaundice) have been seen in patients adjuvant to treatment by radical prostatectomy or taking bicalutamide. Liver function should be assessed radiotherapy.’ periodically. ‘The management of patients with locally advanced, Additional Information non-metastatic prostate cancer for whom surgical castration or other medical intervention is not *From October 2003, bicalutamide 150mg is no longer considered appropriate or acceptable.’ indicated for localised prostate cancer (disease confined to the prostate gland). This is as a Bicalutamide 50mg: consequence of survival data with median follow-up of ‘Treatment of advanced prostate cancer in combination 5 years from the Bicalutamide Early Prostate Cancer with luteinising hormone releasing hormone (LHRH) Programme showing a trend towards an increase in analogue therapy or surgical castration.’ the proportion of deaths in the bicalutamide 150mg Clinical Efficacy group compared with placebo in patients who would otherwise be managed by watchful waiting. The Bicalutamide 150mg: Committee on Safety of Medicines (CSM) has issued Bicalutamide 150mg was compared with castration details of this change (http://medicines.mhra.gov.uk/ (medical or surgical) in two randomised studies in aboutagency/regframework/csm/csmhome.htm). The patients with locally advanced non-metastatic or CSM has also advised that in patients with locally metastatic prostate cancer (n=1450). Follow-up data advanced prostate cancer, the overall risk benefit for a median of 6.3 years in patients with non- remains favourable, although for some patients in this metastatic disease (33%) show no significant group who are at lower risk of disease progression, differences in survival or disease progression between and who are also receiving surgery or radiotherapy, treatments. bicalutamide may not be suitable as an initial therapy. Bicalutamide 50mg: Bicalutamide is taken once daily. At current prices one In patients with advanced disease, bicalutamide 50mg year's treatment costs: in combination with a LHRH analogue (goserelin or £1,669 with bicalutamide 50mg/day leuprorelin) was compared with flutamide plus LHRH £3,129 with bicalutamide 150mg/day analogue in a randomised trial (n=813). At a median £1,590 with goserelin acetate 3.6mg/28 days or follow-up of 160 weeks, no statistically significant 10.8mg/12 weeks. differences were seen between groups in time to progression or death.
Launch dates: May 1995 & June 1999 Manufacturer: AstraZeneca Marketing Authorisation 17901/0005-6 WARNING: This sheet should be read in conjunction with the Summary of Product Characteristics This guidance is based upon the published information available in English at the time the drug was considered. It remains open to review in the event of significant new evidence emerging. A summary sheet with more detailed information can be obtained from MTRAC at the Department of Medicines Management, Keele University, Keele, Staffordshire ST5 5BG Tel: 01782 584131 Fax: 01782 713586 Web: http://mtrac.co.uk RELEVANT NICE GUIDANCE WAS NOT AVAILABLE AT THE TIME OF ISSUE OF THIS VERDICT Date: November 2003 ©Midland Therapeutic Review & Advisory Committee, VS03/17 Department of Medicines Management (THIS VERDICT SHEET REPLACES VS02/12)
SUMMARY SHEET FOR Bicalutamide (Casodex)
For the treatment of prostate cancer
Licensed indication age and general health. Treatment strategies are tailored towards localised, locally advanced, or Bicalutamide 150mg:* advanced (node positive or metastatic) disease. In ‘In patients with locally advanced prostate cancer localised and locally advanced disease, the (T3-T4, any N, M0; T1-T2, N+, M0),’ bicalutamide treatment options are radiotherapy, or radical 150mg ‘is indicated as immediate therapy either prostatectomy.4 Watchful waiting is also sometimes alone or as adjuvant to treatment by radical used in localised disease.6 prostatectomy or radiotherapy.’ Hormonal therapy is the mainstay of treatment in ‘The management of patients with locally advanced, patients with advanced prostate cancer where the non-metastatic prostate cancer for whom surgical aim of treatment is to reduce testosterone castration or other medical intervention is not 4 1 production. Surgical castration by bilateral considered appropriate or acceptable’. orchidectomy can be used although most patients 6 Bicalutamide 50mg: prefer medical castration. The latter can be ‘Treatment of advanced prostate cancer in achieved using luteinising hormone releasing combination with luteinising hormone releasing hormone (LHRH) analogues (buserelin, goserelin, hormone (LHRH) analogue therapy or surgical leuprorelin, and triptorelin), alone or in combination castration.’2 with anti-androgens. Combined use is known as maximal androgen blockade. The anti-androgens *From October 2003, bicalutamide 150mg is no e.g. cyproterone acetate, flutamide, bicalutamide, longer indicated for localised prostate cancer act by blocking the binding of dihydrotestosterone to (disease confined to the prostate gland). This is its receptor thereby preventing androgen action. as a consequence of survival data with median follow-up of 5 years from the Bicalutamide Early Dosage and administration Prostate Cancer Programme showing a trend Bicalutamide 150mg: one tablet taken once daily. towards an increase in the proportion of deaths Treatment at this dose should be taken continuously in the bicalutamide 150mg group compared with 1 for at least 2 years or until disease progression. placebo in patients who would otherwise be managed by watchful waiting. The Committee Bicalutamide 50mg: one tablet taken once daily.2 on Safety of Medicines (CSM) has issued details 3 Clinical efficacy of this change (http://medicines.mhra.gov.uk/aboutagency/regfr Bicalutamide 150mg amework/csm/csmhome.htm). The CSM has Bicalutamide 150mg was compared with castration also advised that in patients with locally (medical or surgical) in two open-label randomised advanced prostate cancer, the overall risk benefit trials in patients with locally advanced non- remains favourable, although for some patients metastatic or metastatic prostate cancer (n=1450).7 in this group who are at lower risk of disease In patients with non-metastatic (T3-T4) disease progression, and who are also receiving surgery (33%), no significant differences in survival or or radiotherapy, bicalutamide may not be 3 disease progression was seen between treatments suitable as an initial therapy. (median follow-up 6.3 years).8 Background information Bicalutamide 50mg The efficacy of bicalutamide in combination with a Prostate cancer is the most common cancer in men LHRH analogue (goserelin or leuprorelin) was in many western countries, and the second leading 4 evaluated in a randomised trial conducted in 813 cause of cancer deaths in men. Every year in the patients with metastatic prostate cancer. Patients UK, approximately 21,000 men are diagnosed with received bicalutamide 50mg once daily or flutamide prostate cancer, and over 10,000 men die from the 5 250mg three times daily, plus concomitant LHRH disease. The aetiology is unknown, although racial therapy (goserelin 3.6mg/28 days or leuprorelin and geographical differences, dietary fat and 7.5mg/28 days). hereditary factors are all implicated. Androgens play a key role in the growth and function of the prostate Interim data with median follow-up of 49 and 95 under both normal and pathological conditions. weeks, and the final analysis (median follow-up 160 weeks) have been published.9-11 At 49 weeks, Current treatment options treatment failure (objective progression, death, or Treatment of prostate cancer depends primarily on withdrawal for any reason) occurred in 42% of the the stage of the disease, but also on the patient’s bicalutamide plus LHRH analogue group and 53% of the flutamide plus LHRH analogue group, p = 0.005. differences were seen between bicalutamide 50mg At 95 weeks the difference between groups in time once daily and flutamide 250mg three times daily in to treatment failure was no longer statistically terms of time to disease progression or death. significant. At 160 weeks, no significant differences The most common adverse events with bicalutamide were seen between treatment groups in time to in clinical trials were gynaecomastia and breast pain. progression or time to death. References Adverse effects 1 AstraZeneca. Casodex 150mg. Summary of Used as monotherapy, the most common adverse Product Characteristics 2003. events with bicalutamide in clinical trials were 2 AstraZeneca. Casodex Tablets 50mg. Summary gynaecomastia and breast pain, compared with hot 7 of Product Characteristics 2001. flushes in the castration groups. 3 Committee on Safety of Medicines. Casodex In combination with a LHRH analogue, the most 150mg (bicalutamide): No longer indicated for common adverse event with bicalutamide and treatment of localised prostate cancer. Letter to flutamide was hot flushes (53%).11 Health Professionals 28 October 2003. (http://medicines.mhra.gov.uk/aboutagency/regfr The Summaries of Product Characteristics (SPCs) amework/csm/csmhome.htm).
Date: November 2003 ©Midland Therapeutic Review & Advisory Committee, SS03/17 Department of Medicines Management (THIS SUMMARY SHEET REPLACES SS02/12)