Case Study Reports

Case Study Reports

Prescribing information can be found on the back pageJob code: FN/2224/2018/UK | Date of preparation: September 2018

All case studies and the information included in them were correct as of February 2014

32

This case study and the information included in it were correct as of February 2014 | Prescribing information can be found on the back page

Mr Bruce Turner RN. BN (Hons), MSc; Dr Anil Joshi MBChB BSc

A patient presenting with high PSA responds well to Firmagon (degarelix)

Author: Mr Bruce Turner RN. BN (Hons), MSc, Uro-Oncology Nurse Practitioner, Homerton University Hospital; Dr Anil Joshi MBChB BSc, Urology Senior House Officer, Homerton University Hospital

Synopsis:

A male in his fifties initially presented with a very raised prostate-specific antigen (PSA) and back pain. He was found to have prostate cancer, Gleason score 4+4, with bone metastases. Following treatment with Firmagon for prostate cancer, his PSA dramatically decreased with alleviation of musculoskeletal pain and no lower urinary tract symptoms.

Case Presentation:

An African-Caribbean male in his fifties was referred to the urology department with a PSA level of 9,000 ng/mL complaining of lumbar back pain. A digital rectal examination revealed a small, firm feeling prostate and normal alkaline phosphatase (ALP) level of 48 μ/L.

An ultrasound scan of the abdomen was performed to exclude hydronephrosis, which was not present, but pelvic lymphadenopathy was. A computed tomography (CT) scan was performed, which showed the presence of extensive para-aortic and iliac lymphadenopathy with mild hydronephrosis but normal renal function. Trans-rectal ultrasound and biopsy of the prostate revealed adenocarcinoma Gleason 4+4 in all cores. Nuclear medicine bone scan revealed bone metastases in the lumbar and sacral spine.

Clinical Management:

The patient began treatment with Firmagon 240 mg subcutaneous injection. After 4 weeks the patient was reviewed and Firmagon 80 mg was administered. A repeat test showed that the patient’s PSA level had dropped to 400 ng/mL and bone pain had resolved.

Apart from some discomfort around the injection site for a few days after administration, the patient reported no treatment-related side effects, carrying on with his normal daily activities and continuing to work.

One month later the patient attended for his next Firmagon 80 mg injection. His PSA level had dropped further to 180 ng/mL and he was asymptomatic. ALP and renal function tests remained within normal parameters. At the 4-week follow-up appointment, a repeat ultrasound scan was performed which showed that the mild hydronephrosis had resolved.

The following month (12 weeks after presentation) the patient attended for his next Firmagon dose and review. He remained asymptomatic and his PSA level had dropped further to 100 ng/mL. He continued to be monitored on a monthly basis. After 16 weeks, his PSA had dropped to 50 ng/mL. Osteoclast activity was checked with urinary N-terminal telopeptide (NTX) but this was normal. He was asymptomatic and bone markers were normal. Bone targeted treatments for metastatic disease were not indicated.

After the sixth dose of Firmagon, his PSA level had dropped to 20 ng/mL and after the seventh treatment it reached 10 ng/mL (nadir).

As of February 2014 (the original date of this case study): The patient currently continues on his present treatment. He is asymptomatic and carries on with his activities of daily living whilst continuing to work. His renal function and bone markers remain normal and he continues to be pain free. The patient was given advice and treatment for erectile dysfunction.

Outcomes and Benefits:

Within 6 months, this patient who initially presented with a PSA of 9,000 ng/mL and back pain became asymptomatic with a substantially reduced PSA of 10 ng/mL (nadir). Due to the patient’s response to treatment and the fact that the patient remains asymptomatic, he continues to receive Firmagon.

Image not of a real patient

54


Mr Bruce Turner RN. BN (Hons), MSc; Dr Anil Joshi MBChB BSc

Discussion:

Metastatic bone disease is a catastrophic complication that can cause problems such as skeletal-related events, hypercalcaemia, anaemia, spinal cord compression and signifies that the malignant process is incurable.1,2 Bone metastases are the most common metastatic deposits in men with prostate cancer3 occurring in 85–100% of men with advanced disease.4

The mainstay of treatment for men in this setting is androgen deprivation therapy. This can be achieved with luteinising-hormone-releasing hormone (LHRH) agonists, gonadotropin-releasing hormone (GnRH) antagonists and/or surgical castration. Most widely used are LHRH agonists. It takes between 7 and 14 days for LHRH agonists to inhibit gonadotropin secretion,5 and the suppression effect of luteinising- hormone synthesis leads to the inhibition of testosterone synthesis.6 This results in an undesirable delay in a patient with, or at risk of, symptoms of metastatic prostate cancer such as bone pain or skeletal-related events.

GnRH receptor antagonists produce rapid androgen deprivation by immediate inhibition of GnRH receptors in the anterior pituitary gland. Klotz et al., (2008) demonstrated that serum testosterone level ≤0.5 ng/mL was achieved within 3 days of commencing treatment in over 95% of patients receiving degarelix, compared with no patients in the leuprolide group.7 This rapid castration was achieved without the need for anti-androgens to prevent tumour flare.7 Klotz et al., (2008) also demonstrated that PSA levels were lower and maintained at a lower level in patients receiving degarelix compared with those receiving leuprolide.7

ALP, as a non-specific marker of osteoblast activity8 is elevated in 70% of patients with bone metastases.9 Schröder and colleagues (2009) compared the activity of degarelix versus leuprolide in controlling the serum ALP levels in men with prostate cancer.10 Patients with metastatic disease in the degarelix group were found to have greater reductions in ALP than the leuprolide group and maintained these lower levels of ALP throughout the study.10

Bone pain can be a common problem in men with advanced prostate cancer but many men will be pain free or see a reduction in bone pain with the appropriate pharmacological treatment. Obstruction of the urinary tract due to malignant ureteric obstruction is associated with poor prognosis.11 This is often caused by lymphadenopathy at the mid-ureter causing extrinsic compression. Malignant obstruction at the vesico-ureteric junction (VUJ) is commonly caused by prostate cancer encasing the VUJ.12

Disclaimer:

The development of this case study report, where a satisfactory therapeutic response to Firmagon was observed, was sponsored by Ferring Pharmaceuticals Ltd, who also sponsored the use of a medical writer for editorial support. Ferring Pharmaceuticals Ltd had no influence on the content of this case study. Any patient identifying information has been changed to ensure anonymity.

Obituary:

Bruce Turner, a well-known and well-loved member of the British Association of Urological Nurses (BAUN) sadly died in December 2016. He left a legacy to establish the BAUN Bruce Turner Award to help urology nurses achieve excellence through education, networking and good practice.

76


Dr Imtiaz Ahmed MBBS, MRCP, FRCR

Treatment with Firmagon (degarelix) for a patient with hormone-dependent prostate cancer and multi-level bony metastasis with associated symptoms

Author: Dr Imtiaz Ahmed MBBS, MRCP, FRCR, Consultant Clinical Oncologist, Southend University Hospital and Spire Healthcare, Southend-on-Sea

Synopsis:

Firmagon rapidly decreased prostate-specific antigen (PSA) and improved symptoms in a 54-year-old patient with severe back pain and mobility complications.

Case Presentation:

A man presented to accident and emergency with a history of back pain, poor urinary stream and constipation. He also had leg weakness with muscle strength of 3/5 in both legs. The patient was unable to walk and required a chest brace for spinal stability.


A magnetic resonance imaging (MRI) scan of his whole spine was taken the day after presentation, which revealed evidence of multi-level metastatic bony deposits and T11 spinal cord compression. A computed tomography (CT) scan taken on the same day showed small but abnormal left para-aortic lymph nodes with evidence of bony metastasis. The liver and the lungs were both clear.

The patient’s presenting PSA level was 318 ng/mL. Therefore a clinical diagnosis of metastatic prostate carcinoma was made. The patient began treatment with oral dexamethasone 8 mg BD and was transferred the next day to a regional radiotherapy centre for initiation of radiotherapy. He also received bicalutamide 50 mg OD with the aim of initiating luteinising-hormone-releasing hormone (LHRH) analogue therapy 12 days later.

Over the next 5 days, the patient’s strength in both legs remained the same, with no improvement despite receiving high-dose steroids and initiating radiotherapy treatment. After a review by the oncology team, it was decided that the patient should be given subcutaneous Firmagon 240 mg. Treatment with bicalutamide was stopped.


Within 24 hours of Firmagon being administered, leg weakness had improved with muscle strength increasing to 4+ on the right leg and 5+ on the left leg. Back pain was alleviated dramatically and pro re nata analgesics were no longer required. Dexamethasone dose was reduced and it was no longer necessary for the patient to wear a chest brace. After completion of radiotherapy a week later, the patient was discharged with monthly Firmagon and no maintenance dexamethasone.

Three months later, the patient’s PSA level had decreased to 1.4 ng/mL. He was no longer in pain, his leg power remained good and no other neurological symptoms were present.

Disclaimer:



98


The management of a patient with advanced prostate cancer and a previous history of myocardial infarction

Author: Dr Heather Payne MBBS, MRCP, FRCR, Consultant in Clinical Oncology, University College London Hospitals

Synopsis:

A 69-year-old patient with advanced metastatic prostate cancer and previous cardiovascular events showed a sustained decrease in prostate-specific antigen (PSA) following treatment with Firmagon (degarelix).

Case Presentation:

A retired computer analyst presented with haematuria. He had no other urinary symptoms. The patient was married with three adult children and two grandchildren. He reported living a very active lifestyle, enjoying hill walking and fishing. He and his wife looked after one grandchild during the week while his son and daughter-in-law went to work.

The patient had a myocardial infarction the previous year and was being treated with clopidogrel, in addition to a statin and ramipril 5 mg. He had made a full recovery from the cardiac event and did not suffer from angina.

It was assumed that the patient’s symptoms were related to the clopidogrel but he was referred to the local urology team as a precaution. He had a cystoscopy, which showed no bladder abnormalities and a digital rectal examination which revealed an enlarged and irregular prostate – the cause of the haematuria.

Further investigations were then carried out for presumed clinical prostate cancer.

The patient’s PSA level measured 67.3 ng/mL and his serum testosterone level was 15.2 nmol/L. Imaging with a magnetic resonance imaging (MRI) scan revealed a locally advanced prostate cancer, stage T4 N1 M1 invading the bladder. The patient’s pelvic lymph nodes were enlarged; the largest measuring 3.7 cm in the external iliac chain. A computed tomography (CT) scan of the chest, abdomen and pelvis demonstrated enlarged para-aortic lymph nodes with the largest measuring 2.7 cm. A bone scan showed metastase in the lumbar spine, ribs and left scapula. He was asymptomatic for all of these lesions.


The patient was referred to the oncology clinic for management and received initial therapy with Firmagon at a loading dose of 240 mg. The evidence from the CS21 study, “The efficacy and safety of degarelix: a 12-month, comparative, randomised, open-label, parallel-group phase III study in patients with prostate cancer” demonstrated that degarelix is non-inferior to the luteinising-hormone-releasing hormone (LHRH) agonist leuprolide, and can achieve an immediate testosterone reduction with a faster reduction in PSA.7 Therefore, for this patient with advanced metastatic prostate cancer, disease in the lymph nodes and bones, and a presenting PSA over 20, control could be achieved more rapidly with degarelix than with an LHRH agonist. In addition, by using degarelix, there was no need for an anti-androgen to protect against testosterone and potential tumour flare – an important consideration for advanced disease with spinal metastases.


The patient tolerated the subcutaneous Firmagon well but did develop a local reaction with erythema around the injection sites. This is common with degarelix and has been reported in up to 40% of men after the initial injections.7 He was warned that these symptoms may occur and the reaction settled after 2 weeks without needing any additional treatment.

Dr Heather Payne MBBS, MRCP, FRCR


1110


After 1 month the patient was reviewed in clinic and was feeling well. His PSA had reduced to a level of 1.6 ng/mL with a serum testosterone level measuring 0.1 nmol/L. He continued receiving Firmagon at a dose of 80 mg every 4 weeks.

An additional analysis of the secondary endpoint of biochemical recurrence rate in the CS21 study (analysed according to baseline characteristics), showed that degarelix reduced PSA levels more rapidly than leuprolide.13 In addition, patients with a baseline PSA level >20 ng/mL were significantly less likely to experience PSA failure with degarelix than with leuprolide.13 The CS21 study followed patients for 1 year of treatment and an extension trial, CS21A, reported data with a further median follow up of 27.5 months.14 This demonstrated that degarelix maintains low levels of testosterone, PSA and follicle-stimulating hormone (FSH), in addition to maintaining lower levels of alkaline phosphatase (ALP) than leuprolide.14

In a post-hoc analysis, patients with baseline PSA level >20 ng/ml had PSA failure rates that were significantly lower with degarelix than leuprolide after 1 year.15 The time for 25% of patients to experience PSA failure or death was significantly longer with degarelix compared with leuprolide (514 vs 303 days, respectively; p=0.01).15 This could equate to PSA failure or death being delayed by approximately 7 months with degarelix treatment as opposed to leuprolide.

As the patient had previously experienced a cardiovascular event, there was a higher risk of further episodes with medical castration therapy, as has been demonstrated for LHRH agonists.

A recent publication by Albertsen et al, (2014) of a retrospective analysis of six clinical trials comparing degarelix with an LHRH agonist included 2,328 men (1,491 treated with degarelix and 837 treated with an LHRH agonist); of these, 31% and 29%, respectively had experienced previous cardiovascular events.16 This analysis showed a reduction in subsequent events for men treated with degarelix for prostate cancer.16

When treated with degarelix, patients with pre-existing cardiovascular disease had significantly fewer cardiovascular events during the first year of treatment with a relative risk reduction of 56% (absolute risk reduction 8.2%), compared with patients treated with an LHRH agonist.16

It was decided to treat this man with ongoing Firmagon.

Discussion:

“After 6 months of therapy, the patient remains well and active with a PSA level measuring <0.01 ng/ml and a testosterone level of 0.1 nmol/L. He did not experience any further injection site reactions. He has experienced the anticipated toxicities of low testosterone levels, with the onset of erectile dysfunction treated with Cialis® (tadalafil) and a vacuum pump. Hot flushes have been alleviated with auricular acupuncture.”

“The patient is being screened with an annual dual-energy X-ray absorptiometry (DEXA) scan for the risk of osteoporosis and is receiving therapy with vitamin D and calcium. He has joined a gym and is undertaking regular resistance exercises to help to maintain muscle and bone strength. He continues to see his cardiologist who has been kept fully informed about the prostate cancer treatments and is monitoring regular lipid and glucose levels. He attends clinic once a month for Firmagon injections and has found it reassuring to be kept under regular review.”

Disclaimer:


Dr Heather Payne MBBS, MRCP, FRCR

1312


Good response and associated increase in quality of life for a patient with metastatic prostate cancer, enrolled into the STAMPEDE trial

Author: Ms Lesley Frew, Clinical Nurse Specialist, Queen Margaret Hospital, Dunfermline

Synopsis:

A 55-year-old patient was treated with Firmagon (degarelix) for metastatic, high-risk prostate cancer. He was subsequently enrolled into the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trial, where he was randomised to receive a non-hormonal treatment and steroids in addition to continuing with Firmagon treatment.

Case Presentation:

This man presented to his GP with lower urinary tract symptoms suggestive of bladder outlet obstruction. A rectal examination conducted by the GP revealed a large, slightly firm prostate that was smooth with no masses. He started receiving alpha-blocker medication and returned to the GP for review during the next month, reporting a slight improvement in symptoms. He was then prescribed an antibiotic for suspected prostatitis and had his PSA level measured, which was found to be 47.6 ng/mL. Given this recording, he was referred to a secondary care urology department in the same month.


Later that month, a digital rectal examination was performed, revealing a very large, hard prostate, which had grown to 85 cm3. Ten sequential biopsies were taken, all testing positive for adenocarcinoma with mixed Gleason scores of 4+3 and 4+4.

These biopsies provided pathological confirmation of prostate cancer. Staging, magnetic resonance imaging (MRI) and bone scans showed pelvic node disease and one metastasis at T9, providing confirmation of metastatic disease. Following diagnosis, the patient experienced an acute episode of urinary retention and was catheterised following emergency hospital admission. Two months after presenting to secondary care (i.e. 1 month after biopsies had been taken), all diagnostic results were discussed at a multidisciplinary meeting and it was agreed that the patient should be treated with Firmagon. He received a 240 mg subcutaneous loading dose on the same day. In addition, the STAMPEDE trial was discussed with the patient who agreed to participate in the trial after speaking with an oncologist. One month later, the patient was referred to the trial team at a cancer centre. He was randomised into a study group receiving Firmagon, with another, non-hormonal treatment and steroids.


The patient’s PSA level continually fell after commencing treatment. Over a 2-month period it decreased from 2.8 ng/mL to <0.1 ng/mL (nadir). He has remained extremely well and is absolutely delighted with how he feels, stating that the treatment he has been given is “gold star”.

Discussion:

“This patient has responded extremely well to a treatment regime including Firmagon. He has shown extremely good tolerance with minimal side effects and as a result, will continue to participate in the STAMPEDE trial.”

Disclaimer:


Ms Lesley Frew


1514


Firmagon (degarelix) treatment showed a rapid and sustained decrease in PSA and testosterone levels following failure with a luteinising-hormone-releasing hormone agonist

Author: Ms Zoe Eastman, Clinical Nurse Specialist, Gloucestershire Hospitals NHS Foundation Trust

Synopsis:

Firmagon rapidly decreased prostate-specific antigen (PSA) and testosterone levels in a patient with metastatic prostate cancer following treatment failure with LHRH agonist therapy.

Case Presentation:

A male in his forties, with a family history of metastatic prostate cancer, presented to his GP with lower urinary tract symptoms. The patient’s PSA level was measured as a precaution and recorded at 209 ng/mL.


The patient was referred to a consultant and a digital rectal examination revealed an enlarged prostate. A biopsy was taken which confirmed extensive Gleason 4+4-level disease. A bone scan and full body computed tomography (CT) scan confirmed bone metastasis in both the 1st and 4th ribs. The patient was initially treated with bicalutamide 150 mg for 1 month.

Two weeks after bicalutamide initiation, he received a luteinising-hormone-releasing hormone (LHRH) agonist injection. By the following month, the patient’s PSA level was 21 ng/mL. The LHRH injections continued for the next 2 months. However, by this point, the patient’s PSA level had increased to 99 ng/mL and testosterone levels were 15 nmol/L. In addition, he was suffering from aching joints and tiredness.

Bicalutamide was reintroduced to help achieve a PSA level of 23 ng/mL and at this point, the consultant applied for funding for Firmagon. Treatment with Firmagon was initiated in the following Spring. Within 1 month, the patient’s PSA level had dropped to 0.1 ng/mL (nadir) and his testosterone level had also dropped to 0.1 nmol/L.


The patient reported physically feeling much better with improved energy levels following treatment initiation with Firmagon. The only side effects experienced were achy joints approximately 3 days after administration and a sore area around the injection site, for which paracetamol was recommended. The patient is still receiving Firmagon and is comfortable with his treatment.

Discussion:

“The use of Firmagon in this patient helped to achieve rapid and sustained decreases in both PSA and testosterone levels, following treatment failure with LHRH agonists. He continues to receive Firmagon and is doing well.”

Disclaimer:


Ms Zoe Eastman


1716


A patient with metastatic prostate cancer, concerned about treatment side effects, shows a rapid and sustained recovery with Firmagon (degarelix)

Author: Mr David Hendry BSc, MBChB, FRCS, FRCS (Urol), Gartnavel General Hospital, Glasgow

Synopsis:

A man with prostate cancer was brought to the hospital by ambulance, following a collapse at home. He presented with a prostate-specific antigen (PSA) level of 716.4 ng/mL, and showed evidence of bone metastases. Although he had initially refused treatment due to concerns about side effects, he agreed to a course of Firmagon. Within 2 months, his PSA level had decreased rapidly and he was able to return to work.

Case Presentation:

A man in his late seventies was diagnosed with prostate cancer in 2010 after presenting with frank haematuria. There was no bone metastasis at the time of diagnosis; however, his PSA level was 126 ng/mL and a Gleason score of 4+4=8 was recorded. The patient also had chronic retention of urine with bladder stones, but refused all treatment due to concerns about side effects. The following year, he was brought to the hospital by ambulance after collapsing at home and was struggling to walk. His PSA and creatinine levels had risen to 716.4 ng/mL and 514 μmol/L, respectively, and a bone scan revealed evidence of bone metastases (stage T4 N1 M1).


The patient agreed to treatment as he felt so unwell and started with Firmagon. Following 1 month of treatment, his PSA and creatinine levels had decreased to 48 ng/mL and 171 μmol/L, respectively. A repeat test 3 weeks later showed that his PSA level had reduced to 2.2 ng/mL and he was able to return to work. After 4 months of treatment, his PSA level was undetectable (<0.1 ng/mL) and his creatinine level was 151 μmol/L. Following 27 months of treatment, the patient’s PSA level remained undetectable at <0.1 ng/mL.


The patient’s PSA level decreased markedly within 2 months of commencing treatment with Firmagon, and the patient was able to return to work. After 27 months, his PSA level was undetectable (<0.1 ng/mL). The patient reported no side effects relating to Firmagon; he remains well and has now retired.

Discussion:

Given the acute presentation with renal failure and bone metastases, Firmagon was offered in order to avoid the issues of potential testosterone flare associated with a luteinising-hormone- releasing hormone (LHRH) agonist.7 It is reassuring for both patient and clinician to see a rapid improvement in all the key parameters, such as creatinine and PSA levels. This particular patient was very concerned about the potential side effects of treatment, and had declined a transurethral resection of the prostate (TURP) and litholapaxy as he was concerned about the risk of urinary incontinence. Over the year leading up to his emergency presentation he had continued to attend the outpatient clinic where there was concern about his rising PSA (it reached a level of 488 ng/mL). Again, as he was feeling well, he did not want to have the side effects of androgen deprivation. With Firmagon he has been fortunate in that he has had no issues with hot flushes or any local skin/injection site reaction.

Disclaimer:


Mr David Hendry BSc, MBChB, FRCS, FRCS (Urol)


1918


A patient presenting with urinary tract symptoms and a high PSA level returns to his normal active lifestyle after treatment with Firmagon (degarelix)

Author: Ms Julie Rawlings, Research Nurse, Castle Hill Hospital, Hull

Synopsis:

A man in his late seventies was referred to the prostate assessment clinic with urinary tract symptoms and a prostate-specific antigen (PSA) level of 150 ng/mL. After unsuccessful initial treatment with leuprorelin, he began a course of Firmagon that rapidly decreased his PSA and testosterone levels. During the 8 months that he received Firmagon, his symptoms improved and he was able to return to his physically active lifestyle.

Case Presentation:

A 78-year-old man presented to his GP with lower urinary tract symptoms, including haematuria. He had a history of intermittent symptoms and a slightly raised PSA level. He was consequently referred to the prostate assessment clinic.


At the clinic, his PSA was found to have risen to 150 ng/mL and a digital rectal examination (DRE) recorded a benign-feeling tumour. A prostate biopsy revealed adenocarcinoma with a Gleason score of 4+4=8 for a left lobe nodule and 3+4=7 for the right lobe, confirming prostate cancer. A bone scan showed multiple metastases to cervical, thoracic and lumbar vertebrae, as well as the ribs, pelvis, humeri and femur. All appeared as diffuse metastatic disease. A computed tomography (CT) scan was also performed, but showed no evidence of lymphadenopathy. At this stage, the patient also complained of bone pain in his shoulder and back.

A pre-treatment measurement showed that the patient’s PSA level had increased to 350 ng/mL. He was then initially treated with bicalutamide 50 mg OD. After 2 weeks, with a PSA measurement of 79 ng/mL, the patient received a first injection of leuprorelin 3.75 mg. He also consented to enter a clinical trial in which he was randomised to receive a 4-week course of radiotherapy to the prostate.

Two weeks following the first injection of leuprorelin, the patient’s PSA level had fallen to 18 ng/mL, and after a further 2 weeks it had fallen to 16 ng/mL. However, his testosterone level remained above castrate levels at 7.9 nmol/L. After another 7 weeks, the patient’s PSA level had dramatically increased to 290 ng/mL with testosterone at 10 nmol/L.

The patient’s test results were subsequently reviewed at a multidisciplinary team (MDT) meeting and it was decided to initiate treatment with Firmagon immediately. The patient received a loading dose of 240 mg, followed by 80 mg every 4 weeks. Two weeks after the loading dose, the patient’s PSA level had decreased to 86 ng/mL with testosterone at a castrate level of 2.9 nmol/L. Over the following 5 months, PSA and testosterone levels continued to drop, ultimately reaching 12 ng/mL (nadir) and 1.4 nmol/L (nadir), respectively.

Following 8 months of treatment with Firmagon, the patient’s PSA and testosterone levels once again began to increase. It was decided to cease Firmagon treatment after a PSA measurement of 37 ng/mL was recorded, and proceed with surgical castration by total orchidectomy. Since undergoing surgery, the patient’s PSA level has increased to 73 ng/mL, with testosterone levels remaining at 0.7 nmol/L.

Ms Julie Rawlings


2120



After commencing treatment with Firmagon, this patient’s PSA level continually fell over a period of 8 months, with mild injection site reactions being the only side effects. When the patient first presented, he had lost weight, had a poor appetite and was unable to enjoy physical activity. After receiving Firmagon, he regained weight, his appetite improved and he was able to return to a physically active lifestyle, including playing golf regularly.

Discusson:

Treatment with Firmagon helped this patient achieve rapid and sustained reductions in PSA and testosterone levels. It slowed his disease progression with few side effects and he was able to continue a pain-free, normal and active lifestyle for a further 8 months that he may not have otherwise enjoyed.

Disclaimer:


Ms Julie Rawlings

A patient presenting with a pathological humerus fracture and a high PSA level achieves a rapid PSA reduction and improved quality of life after treatmentwith Firmagon (degarelix)

Author: Mr Samas Salihu, Uro-oncology Clinical Nurse, Royal Liverpool and Broadgreen University Hospitals NHS Trust

Synopsis:

A man in his late sixties, who had previously been catheterised because of urinary retention, presented with a pathological fracture of the humerus and a prostate-specific antigen (PSA) level of 22,000 ng/mL. The patient received treatment with Firmagon immediately and within a few months his PSA level had dropped substantially and his urinary retention had resolved. His quality of life subsequently improved allowing him to enjoy life with his family and return to work.

Case Presentation:

A 67-year-old man with a family history of prostate cancer presented to accident and emergency with acute urinary retention and was referred to a urologist. He had a catheter inserted and was sent home with tamsulosin and finasteride. His PSA level was not measured because a digital rectal examination (DRE) revealed a benign feeling prostate. A year later, his GP contacted the urology specialist registrar with a query regarding an X-ray of the patient’s humerus, which appeared to show a pathological fracture. The GP was advised to measure the patient’s PSA, which was recorded as 22,000 ng/mL and he was referred to the uro-oncology clinic.

Mr Samas Salihu


2322



A bone scan was performed at the clinic, which showed multiple bony metastases and a diagnosis of metastatic prostate cancer was confirmed. The patient began treatment with 240 mg of Firmagon immediately. He was also prescribed zoledronate to prevent any further skeletal fractures. Within 2 months of starting Firmagon treatment, the patient had returned to work, and after a further 2 months, his PSA level had decreased to 366 ng/mL. He reported that his pain had gone and his appetite had returned; he could also urinate normally so his catheter was removed and surgery was not required.

The patient’s PSA level continued to decrease steadily, but the following year it rose to 964 ng/mL and the patient was prescribed bicalutamide alongside Firmagon. The patient’s PSA level responded slowly to this change in treatment, so he was referred to the uro-oncology clinic. At the clinic, a repeat bone scan was performed which showed extensive osteoblastic metastases with a slight improvement in appearance, but no new lesions were observed. The patient was recommended to continue with Firmagon, but also to start a course of systemic palliative chemotherapy with docetaxel, to which he agreed.

After 1 month, his PSA level had fallen to 339 ng/mL and within 7 months it had decreased to 50 ng/mL. Following this reading, his PSA level once again began to rise and within 3 months had reached 301 ng/mL. Whilst continuing with Firmagon, the patient also began treatment with enzalutamide. Within 2 months, his PSA level had dropped to 3.1 ng/mL (nadir).

Mr Samas Salihu


Treatment of this patient with Firmagon resulted in a rapid and substantial decrease in PSA level and a considerable improvement in his quality of life (QoL). He was able to urinate normally after a few months and return to work. The only side effect experienced by this patient was erectile dysfunction, which was treated with tadalafil. After 2 months of Firmagon treatment the patient reported “I feel great in myself; no pain, my appetite is back and I can do more now”. The patient has since been able to go on a cruise and recently got married.

Discussion:

“This patient experienced a rapid decrease in PSA level over a few months, together with a considerable improvement in his QoL. Since working with Firmagon, I have been very impressed with the swift effect that it has on patients’ physical symptoms and biochemical readings. I consider Firmagon a valuable addition to the treatments available to patients with prostate cancer, and a key alternative for those who are unable to tolerate other therapies.”

Disclaimer:


2524


A patient with stage T3b prostate cancer, unable to tolerate the side effects of LHRH agonists and anti-androgen therapy, shows improvement with Firmagon (degarelix)

Author: Ms Helen Showler, Uro-oncology Specialist Nurse, Newcastle-upon-Tyne Hospitals NHS Trust

Synopsis:

A 58-year-old man with stage T3b prostate cancer was treated with Firmagon following an inability to tolerate the side effects of a luteinising-hormone-releasing hormone (LHRH) agonist and anti-androgen therapy. The patient has been receiving monthly injections of Firmagon and has shown no evidence of metastatic disease.

Case Presentation:

A 58-year-old man was invited for a prostate-specific antigen (PSA) test as part of ProtecT, a randomised, controlled trial to evaluate treatments for clinically localised prostate cancer. However, the results revealed a PSA level of 68.9 ng/mL. A prostate biopsy revealed adenocarcinoma with a Gleason score of 7, and a computed tomography (CT) scan showed an enlarged left internal iliac node, but no other significant lymphadenopathy. He was diagnosed with stage T3b locally advanced prostate cancer and was therefore ineligible to continue in the trial.


The patient was seen by the urology team and offered standard treatment with an LHRH agonist or entry into the GENTAX study comparing an LHRH agonist alone with an LHRH agonist following up-front taxotere chemotherapy.17 The patient consented to be enrolled onto the study and was randomised to receive LHRH agonist only. After commencing treatment, his PSA level decreased to 2.54 ng/mL.

However, at a routine appointment the following year, he reported experiencing significant toxicities as a result of the treatment. He reported low mood, depression, lethargy and he felt he had no quality of life. At this stage, his PSA level was 1.4 ng/mL, with a testosterone level of 1.9 nmol/L. His treatment was then switched to an anti-androgen, bicalutamide, and his PSA level dropped further to 0.44 ng/mL (nadir). At his next follow-up appointment, he reported that he had noticed a significant improvement in his general mood and energy levels and was able to play sports and enjoy time with his wife and son.

The next year, a significant increase in the patient’s alanine aminotransferase level was recorded. There was no evidence of infective hepatitis and a liver ultrasound showed no abnormality, so bicalutamide therapy was discontinued. The patient was reluctant to return to treatment with LHRH agonists and was therefore placed under surveillance to initiate intermittent hormones should his PSA level begin to rise. Two months later, a CT scan of the thorax, abdomen and pelvis showed simple cysts and haemangioma in the liver, but no evidence of liver metastases or recurrent disease.

After 4 months, his PSA level had increased to 8.5 ng/mL, so treatment with bicalutamide was restarted. Within 2 weeks his PSA had dropped to 6 ng/mL, but the results of his liver function tests were elevated and the treatment was discontinued. He continued to have regular PSA checks and several months later his PSA level had risen to 15.9 ng/mL. It was not possible to restart treatment with LHRH agonists as the patient could not tolerate anti-androgen therapy and there would be a risk of testosterone flare.7 Therefore, permission was requested to initiate treatment with Firmagon, which was granted.

Within 1 month of starting Firmagon treatment, the patient’s PSA level had decreased to 6.5 ng/mL, and after another month it had decreased further to 2.8 ng/mL. One year after first receiving Firmagon, his PSA level reached a nadir of 0.5 ng/mL. The patient has now been receiving Firmagon for almost 5 years and has had regular CT and bone scans. None of these scans have provided evidence of metastasis. He has also had no further liver function problems since receiving Firmagon. His PSA level has recently begun to rise and his latest reading was 9.2 ng/mL. However, his latest CT scan still provided no evidence of nodal or metastatic disease.

Ms Helen Showler


2726



The patient continues to have monthly injections of Firmagon and remains well. Initially, he was anxious and had monthly PSA and liver function tests as he was aware that prior to Firmagon treatment, there was little that could be done without the use of anti-androgens. He tolerated Firmagon well, but experienced some common side effects including pain and discomfort at the injection site, and flu-like symptoms approximately 12 hours following injection.7 No treatment was administered for the injection site discomfort, but the flu-like symptoms were treated with paracetamol. He also found that these symptoms improved if the Firmagon was injected more slowly. Importantly, the patient has reported that he no longer experiences the same debilitating side effects that he had with the LHRH agonist.

Discussion:

Had Firmagon treatment not been available, this patient would have been unable to recommence LHRH agonist treatment without risk of tumour flare occurring due to giving the LHRH agonist without anti-androgen cover.7 He has always required a lot of psychological support and would have coped badly with a prognosis of being unable to receive treatment.

Disclaimer:


Ms Helen Showler

References:

1. Coleman RE. Skeletal complications of malignancy. Cancer 1997;80:1588–94. 2. Mundy GR. Introduction. In: Continuity of Care in Metastatic Prostate Cancer. Drudge-Coates L,editors. London: Novartis;

2006, pp 5.3. Hatoum HT, Lin SJ, Smith MR et al. Zoledronic acid and skeletal complications in patients with solid tumors and bone

metastases: analysis of a national medical claims database. Cancer 2008;113:1438–45. 4. Desai B, Rogers MJ, Chellaiah MA. Mechanisms of osteopontin and CD44 as metastatic principles in prostate cancer cells.

Mol Cancer. 2007;6:1–16.5. Conn PM, Crowley WF. Gonadotropin-releasing hormone and its analogues. N Engl J Med. 1991;324:93–103. 6. Wilson S, Crawford E. Endocrine manipulation. In: Urological Oncology. Nargund V, Raghavan D, Sandler H, editors. London:

Springer ; 2008, pp 518–35.7. Klotz L, Boccon-Gibod L, Shore ND et al. The efficacy and safety of degarelix: a 12-month, comparative, randomized,

open-label, parallel-group phase III study in patients with prostate cancer. BJU Int. 2008;102:1531–8.8. Cook RJ, Coleman R, Brown J et al. Markers of bone metabolism and survival in men with hormone-refractory metastatic

prostate cancer. Clin Cancer Res. 2006;12:3361–7.9. Wolff JM, Ittel TH, Borchers H et al. Metastatic workup of patients with prostate cancer employing alkaline phosphatase

and skeletal alkaline phosphatase. Anticancer Res. 1999;19:2653–5.10. Schroder FH, Tombal B, Miller K et al. Changes in alkaline phosphatase levels in patients with prostate cancer

receiving degarelix or leuprolide: results from a 12-month, comparative, phase III study. BJU Int. 2010;106:182–7. 11. Ishioka J, Kageyama Y, Inoue M et al. Prognostic model for predicting survival after palliative urinary diversion

for ureteral obstruction: analysis of 140 cases. J Urol. 2008;180:618–21. 12. Uthappa M, Kellett M. Interventional radiology in malignant urinary tract obstruction. In: Interventional Radiology in Cancer.

Adam A, Dondelinger R, Mueller P, editors. London: Springer-Verlag; 2004, pp 155–65. 13. Tombal B, Miller K, Boccon-Gibod L et al. Additional analysis of the secondary end point of biochemical recurrence rate

in a phase 3 trial (CS21) comparing degarelix 80 mg versus leuprolide in prostate cancer patients segmented by baseline characteristics. Eur Urol. 2010;57:836–42.

14. Crawford ED, Tombal B, Miller K et al. A phase III extension trial with a 1-arm crossover from leuprolide to degarelix: comparison of gonadotropin-releasing hormone agonist and antagonist effect on prostate cancer. J Urol. 2011;186:889–97.

15. Shore N, Moul J, Crawford E et al. Prostate-specific antigen (PSA) progression-free survival (PFS): A comparison of degarelix versus leuprolide in patients with prostate cancer. J Clin Oncol. 2011;29:(suppl 7; abstr 12).

16. Albertsen PC, Klotz L, Tombal B et al. Cardiovascular morbidity associated with gonadotropin releasing hormone agonists and an antagonist. Eur Urol. 2014;65:565–73.

17. Pedley ID, Frew JA, Wilson JM, et al. Tolerability and efficacy of anti-androgen manipulation versus taxotere and anti-androgen manipulation in patients with hormone-naive, highrisk/ metastatic prostate cancer : A phase II, open-labeled, randomized study. J Clin Oncol. 29:2011 (suppl 7; abstr 147).

Prescribing Information:

Firmagon® (degarelix) 120mg and 80mg powder and solvent for solution for injection. Please consult the full Summary of Product Characteristics before prescribing. Name of Product: Firmagon 120mg and 80mg powder and solvent for solution for injection. Composition: Each vial contains 120mg or 80mg degarelix (as acetate). Indication: Firmagon is a gonadotrophin releasing hormone (GnRH) antagonist indicated for treatment of adult male patients with advanced hormone-dependent prostate cancer. Dosage and administration: For subcutaneous use only. Starting dose–240mg administered as two subcutaneous injections of 120mg each. Maintenance dose – 80mg administered monthly as one subcutaneous injection. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Special Warnings and Precautions: Long-term androgen deprivation therapy may prolong the QT interval. The benefit/risk ratio must be thoroughly appraised in patients with a history of a corrected QT interval over 450 msec, in patients with a history of or risk factors for torsades de pointes and in patients receiving concomitant medicinal products that might prolong the QT interval as Firmagon has not been studied in these patients. A thorough QT study showed that there was no intrinsic effect of Firmagon on QT/QTc interval. Monitoring of liver function in patients with known or suspected hepatic disorder is advised during treatment. Firmagon has not been studied in patients with severe renal impairment, patients with a history of severe untreated asthma, anaphylactic reactions or severe urticaria, or angioedema. It can be anticipated that long periods of testosterone suppression in men will have effects on bone density. Diabetic patients may require more frequent monitoring of blood glucose when receiving androgen deprivation therapy. Cardiovascular disease such as stroke and myocardial infarction has been reported in the medical literature in patients with androgen deprivation therapy. Therefore, all cardiovascular risk factors should be taken into account. Side effects: Very Common: hot flush, injection site adverse reactions.

Common: anaemia, weight increase, insomnia, dizziness, headache, diarrhoea, nausea, liver transaminases increased, hyperhidrosis (incl. night sweats), rash, musculoskeletal pain and discomfort, gynaecomastia, testicular atrophy, erectile dysfunction, chills, pyrexia, fatigue, Influenza-like illness. Uncommon: hypersensitivity, hyperglycemia/ diabetes mellitus, cholesterol increased, weight decreased, appetite decreased, changes in blood calcium, depression, libido decreased, mental impairment, hypoaesthesia, vision blurred, cardiac arrhythmia (incl. atrial fibrillation), palpitations, QT prolongation, hypertension, vasovagal reaction (incl. hypotension), dyspnoea, constipation, vomiting, abdominal pain, abdominal discomfort, dry mouth, bilirubin increased, alkaline phosphatase increased, urticaria, skin nodule, alopecia, pruritus, erythema, osteoporosis/osteopenia, arthralgia, muscular weakness, muscle spasms, joint swelling/stiffness, pollakiuria, micturition urgency, dysuria, nocturia, renal impairment, incontinence, testicular pain, breast pain, pelvic pain, genital irritation, ejaculation failure, malaise, peripheral oedema. Rare: neutropenic fever, anaphylactic reactions, myocardial infarction, cardiac failure. Please consult the full Summary of Product Characteristics for further information about side effects. Presentation: Firmagon 120mg contains 2 vials of 120mg powder for solution for injection and 2 solvent prefilled syringes, 2 vial adaptors and 2 administration needles. Firmagon 80mg contains 1 vial of 80mg powder for solution for injection and 1 solvent pre-filled syringe, 1 vial adaptor and administration needle. Solvent for both 120mg and 80mg: Water for injection. Marketing Authorisation Number: 80mg: EU/1/08/504/001, 120mg: EU/1/08/504/002. Marketing Authorisation Holder: Ferring Pharmaceuticals A/S, Kay Fiskers Plads 11, DK-2300 Copenhagen S, Denmark. Legal category: POM. Basic NHS price: Firmagon 120mg - £260.00; Firmagon 80mg - £129.37 Date of preparation: July 2018. Firmagon® is a registered trademark. PI Job Code: FN/1250/2018/UK(1).

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to

Ferring Pharmaceuticals Ltd. Tel: 0800 111 4126. Email: [email protected]

Job code: FN/2224/2018/UK | Date of preparation: September 2018

Documents

Case Study Reports