Download Prostate NICaN SACT CMG Version 2.0 June 2016 FINAL

Reference No:
Title:
Systemic anti cancer therapy (SACT) clinical management
guidelines for Advanced/metastatic Prostate Cancer
Author(s)
Dr Darren Mitchell Consultant Clinical Oncologist on behalf of the
Genitourinary oncology group. Belfast City Hospital
Ownership:
NICaN
Approval by:
NICaN Drugs & Therapeutics
committee
Approval
date:
June 2016
Operational
Date:
July 2018
Next
Review:
July 2018
Version No.
2.0
Supersedes 1.0
Links to
NICaN Prostate SACT protocols
other policies
Version control for drafts:
Date
Version
Author
Comments
2/12/2013
1.0
Dr D Mitchell
Final version issued
June 2016
2.0
Dr D Mitchell
Updated to reflect new NICE guidance
SACT for Prostate Cancer v2.0
Page 1 of 12
Authorisation of Systemic Anti-Cancer Therapy (SACT) Guidelines for
Prostate Cancer
These SACT guidelines are being submitted by the author on behalf of the
Genitourinary Oncology group.
SACT for Prostate Cancer v2.0
Page 2 of 12
1.0
INTRODUCTION / PURPOSE OF POLICY
1.1
Background
Prostate cancer which has metastasized may be seen either at the time of
initial diagnosis or following radical treatment for localised or locally advanced
disease which subsequently demonstrates evidence of metastatic disease.
In either scenario the mainstay of initial treatment is with hormonal
manipulation which can maintain disease control for many years.
Once there is evidence of progressive disease despite hormonal manipulation
the disease is termed ‘castration resistant’ and the aim of management is to
maintain quality of life and prolongation of survival were possible with
systemic therapy, palliative radiotherapy, palliative radionucleotide therapy
and palliative care input.
1.2
Purpose
To ensure consistent use of SACT for patients with Prostate cancer.
2.0
SCOPE OF THE POLICY
This document is aimed at all clinical staff involved in the management of
patients receiving SACT for Prostate cancer.
3.0
ROLES/RESPONSIBILITIES
It is the responsibility of all clinical staff involved in the management of
patients receiving SACT for Prostate cancer to familiarise themselves with
these guidelines.
SACT for Prostate Cancer v2.0
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4.0
KEY POLICY PRINCIPLES
The treatment options for metastatic prostate cancer are tabulated below.
Diagnosis within
3/12 and fit for Upfront Docetaxel
(hormone
sensitive)
Diagnosis >3/12 or
not fit for Docetaxel
1st line
2nd line
3rd line
ADT
Up-front
Docetaxel
Enzalutamide
Or
Abiraterone (TA259)
Or
Cabazitaxel
Enzalutamide (TA 377)
Or
Abiraterone (TA 387)
Radium (TA 376)
Consider re challenge
Docetaxel or
MItoxantrone
ADT
Rapid CRPC and
fit for Docetaxel
ADT
Docetaxel
Pt not suitable for
docetaxel 75, still
suitable for chemo
Not suitable for
chemo
ADT
Enzalutamide (TA377)
Or
Abiraterone (TA 387)
Enzalutamide (TA 377)
Or
Abiraterone (TA 387)
ADT
Docetaxel (if fit)
Consider Weekly
docetaxel or
Mitoxantrone
Enzalutamide (TA
316)
Or
Abiraterone (TA 259)
Or
Cabizitaxel
Docetaxel weekly
MItoxantrone
4th line
5th line
Enzalutamide (TA 316)
Or
Abiraterone (TA 259)
Radium (TA
376)
Radium (TA 376)
Consider re challenge
Docetaxel or
MItoxantrone
Radium (TA
376)
Enzalutamide (TA 316)
Or
Abiraterone (TA 259)
Radium (TA
376)
4.1.1 Docetaxel
The use of Docetaxel chemotherapy in men with prostate cancer can be considered
in two clinical scenarios.
1) Docetaxel chemotherapy has been classically used in men with advanced
prostate cancer who have become resistant to ADT. These men have either
symptomatic progression or rapid PSA progression in the absence of
symptoms having previously received androgen deprivation therapy. It is
NICE approved in this scenario (NICE TA101). (1-2)
2) The use of docetaxel in hormone naïve metastatic/high risk prostate cancer
(within 12weeks of commencing ADT) has recently been recognised in two
large randomised studies to provide a significant improvement in overall
survival when compared to men receiving hormone treatment alone at
diagnosis. (3-4)
Docetaxel in this ‘up-front’ role is an 'off label use' but NICE guidance is
available to recommend its use. (Clinical Commissioning Policy Statement:
Docetaxel in combination with androgen deprivation therapy for the treatment
of hormone naïve metastatic prostate cancer. NHS England Reference:
[B15/PS/a].) (NICE ESUOM50 (Evidence Summaries Unlisensed or Off label
Medicines))
SACT for Prostate Cancer v2.0
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The side effects of docetaxel can be substantial and it may not be possible to
use docetaxel if the disease has progressed to a stage where it is causing
significant symptoms.
Some men who may not tolerate docetaxel at the 75mg/m2 21D regimen may
tolerate the 30mg/m2 weekly (5/6) scheduling as it appears to have a better
toxicity profile. It should however be noted that it does not provide a
significantly better survival benefit than Mitoxantrone + Prednisolone which
was inferior to the Docetaxel 75mg/m2. (1)
Patient selection
1 Metastatic castration resistant prostate cancer with clinical and or
biochemical progression
ECOG performance status ≤ 2 (KPS >60)
Satisfactory renal function (CrCl > 60ml/min)
Satisfactory haematinics
Adequate hepatic and cardiac function
2 Hormone naïve metastatic prostate cancer for:
 Men either commencing, or who have commenced within 12 weeks, long-term
ADT for metastatic disease for the first time; and
 Men of sufficient performance status to be treated with 6 cycles of docetaxel
chemotherapy.
ECOG performance status ≤ 2 (KPS >60)
Satisfactory renal function (CrCl > 60ml/min)
Satisfactory haematinics
Adequate hepatic and cardiac function
Treatment regimen
Docetaxel PROST
Docetaxel 75mg/m2 D1 in combination with prednisolone 10mg/day on a
21day cycle planned for up to 10 cycles pending response. (maximum of 6
cycles in the ‘up front’ regimen)
It should be discontinued if severe adverse advents occur or in the presence
of progression of disease as evidenced by clinical or laboratory criteria, or by
imaging studies.
SACT for Prostate Cancer v2.0
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Follow-up
As clinically directed
PSA 3 monthly.
4.1.2 Abiraterone
Abiraterone (5-6) in combination with prednisolone is recommended (TA 259)
as an option for the treatment of castration-resistant metastatic prostate
cancer in adults, if:

their disease has progressed on or after one docetaxel-containing
chemotherapy regimen,
and

the manufacturer provides Abiraterone with the discount agreed in the
patient access scheme.
It can be used in combination with prednisone or prednisolone is within its
marketing authorisation, as an option for treating metastatic hormonerelapsed prostate cancer:

in people who have no or mild symptoms after androgen deprivation therapy
has failed, and before chemotherapy is indicated (TA 387)

only when the company rebates the drug cost of abiraterone from the 11th
month until the end of treatment for people who remain on treatment for more
than 10 months. (3-4)
Abiraterone is maintained until evidence of progressive disease.
Patient selection
As above
As above
ECOG performance status ≤ 2
Satisfactory renal function (CrCl > 60ml/min)
Satisfactory haematinics
Adequate hepatic function
Adequate blood pressure control
Treatment regimen
Abiraterone acetate 1000mg (4x250mg tablets) po od plus prednisolone ec
5mg po bd continuously
SACT for Prostate Cancer v2.0
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Follow-up
As clinically directed
PSA 3 monthly.
4.1.3 Mitoxantrone
Mitoxantrone chemotherapy in combination with prednisolone has been
demonstrated to improve quality of life and disease response in men with
metastatic castration resistant prostate cancer. No improvement in overall
survival has been demonstrated with this combination and it was found to
provide inferior overall survival when compared to 3weekly Docetaxel (1-2). Its
use as primary chemotherapy in castration resistant disease is therefore
limited to men with a contra-indication to Docetaxel.
It has been used in the TROPIC clinical trial post Docetaxel as a comparator
to Cabazitaxel and is noted to achieve PSA control in approx 17% of men (7).
However overall survival was inferior when compared to Cabazitaxel..
Patient selection
Patient has castration resistant prostate cancer with either symptomatic
progression or rapidly rising PSA.
ECOG performance status ≤ 2
Docetaxel chemotherapy is contra-indicated or patient has progressed on or
following previous Docetaxel chemotherapy
Satisfactory renal function (CrCl > 60ml/min)
Satisfactory haematinics
Adequate hepatic and cardiac function
Treatment regimen
Mitox/pred
Mitoxantrone 12mg/m2 iv infusion in 100ml N/Saline over 15 mins on day 1
only.
Prednisolone e/c 5mg bd orally continuously during treatment. 21 day cycle
Follow-up
As clinically directed
PSA 3 monthly
SACT for Prostate Cancer v2.0
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4.1.4 Enzalutamide
Enzalutamide (8-9) Is indicated in metastatic castration resistant prostate
cancer.
Either:
In men who have no or mild symptoms after androgen deprivation therapy has
failed, and before chemotherapy is indicated (9) (provided the company
supplies it with the discount agreed in the patient access scheme).
[Enzalutamide for treating metastatic hormone-relapsed prostate cancer
before chemotherapy TA377]
Or
In men with metastatic castration resistant prostate cancer whose disease has
progressed during or after docetaxel containing chemotherapy (8). (If the
manufacturer provides
enzalutamide with the discount agreed in the patient access scheme) [TA316]
Patient selection
As above
ECOG performance status ≤ 2
Satisfactory renal function (CrCl > 60ml/min)
Satisfactory haematinics
Adequate hepatic function
Adequate blood pressure control
Treatment regimens
Enzalutamide
Enzalutamide 160mg od on a 28day cycle
Follow-up
As clinically directed
PSA 3 monthly
SACT for Prostate Cancer v2.0
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4.1.5 Zolendronic Acid.
Bisphosphonates for pain relief may be considered for men with hormonerefractory prostate cancer when other treatments (including analgesics and
palliative radiotherapy) have failed. (NICE)
Bisphosphonates are not recommended for use in men with hormonerefractory prostate cancer for the prevention of bone metastases or to prevent
or reduce the complications of bone metastases.
Bisphosphonates are not recommended in the prevention of osteoporosis in
men on androgen deprivation therapy. (NICE)
Careful attention to renal function in this patient group is required and in view
of risk of osteonecrosis of mandible, dental examination should be considered
and appropriate preventative treatment prior to treatment in patients with
concomitant risk factors.
RADIUM 223
Radium 223 (10) is NICE approved for men who have had Docetaxel for
Metastatic castration resistant prostate cancer and have symptomatic bone
metastasis and no visceral metastasis. (NICE TA 376)
Eligibility Criteria
•
Patient has symptomatic metastatic castration resistant prostate cancer
•
Previously treated with docetaxel chemotherapy
•
ECOG performance status ≤ 2
•
Satisfactory haematinics
Cabazitaxel
Cabazitaxel in combination with prednisone or prednisolone (7) has recently
been recommended by NICE (TA391) as an option for treating metastatic
hormone-relapsed prostate cancer in people whose disease has progressed
during or after docetaxel chemotherapy. The guidance does not cover patients
who have had docetaxel followed by either enzalutamide, abiraterone or
radium.
It can be offered if:

the person has an eastern cooperative oncology group (ECOG) performance
status of 0 or 1

the person has had 225 mg/m2 or more of docetaxel
SACT for Prostate Cancer v2.0
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
treatment with cabazitaxel is stopped when the disease progresses or after a
maximum of 10 cycles (whichever happens first)

NHS trusts purchase cabazitaxel in pre-prepared intravenous-infusion bags,
not in vials, and

the company provides cabazitaxel with the discount agreed in the patient
access scheme.

Treatment regimens

Cabazitaxel 25mg/m2 every 3weeks in combination with prednisolone.
It should be discontinued if severe adverse advents occur or in the presence
of progression of disease as evidenced by clinical or laboratory criteria, or by
imaging studies.
Follow-up
As clinically directed
PSA 3 monthly.
5.0
IMPLEMENTATION OF POLICY
5.1
Dissemination
This policy will be agreed by all consultant oncologists treating patients with
SACT for Bladder cancer. The guideline will form the basis for development of
the SACT regimen specific protocols. It will be available on the intranet for use
by all doctors, nurses and pharmacists involved in all stages of SACT
assessment and delivery in patients with bladder cancer.
6.0
MONITORING
Use of these guidelines will be monitored using audit.
SACT for Prostate Cancer v2.0
Page 10 of 12
7.0
EVIDENCE BASE / REFERENCES
NICE CG175 Prostate cancer: full clinical guideline
http://www.nice.org.uk/nicemedia/live/14348/66232/66232.pdf
1 Tannock IF, de Wit R, Berry WR et al Docetaxel plus Prednisone or
Mitoxantrone plus Prednisone for Advanced Prostate Cancer. New Eng J Med
2004; 351: 1502-1512
2 Berthold DR, Pond GR, Soban F et al. Docetaxel Plus Prednisone or
Mitoxantrone Plus Prednisone for Advanced Prostate Cancer: Updated
Survival in the TAX 327 Study JCO 2008; 26: 242-245
3 James ND,et al. Addition of docetaxel, zoledronic acid, or both to first-line
long-term hormone therapy in prostate cancer (STAMPEDE): survival results
from an adaptive, multiarm, multistage, platform randomised controlled trial.
The Lancet http://www.thelancet.com/pdfs/journals/lancet/PIIS01406736(15)01037-5.pdf
4 Sweeney CJ, Chen Y, Cardussi M et al Chemohormonal Therapy in
Metastatic Hormone-Sensitive Prostate Cancer. NEJM 2015; 373: 737-746
5 Abiraterone for castration resistant metastatic prostate cancer previously
treated with a docetaxel-containing regimen. NICE technology appraisal
guidance 259 (2012)
http://www.nice.org.uk/nicemedia/live/13775/59723/59723.pdf
6 de Bono JS, Logothetis CJ, Molina A et al Abiraterone and Increased
Survival in Metastatic Prostate Cancer. N Engl J Med 2011; 364:1995-2005
7 de Bono JS, Oudard S, Ozguroglu M et al. Prednisone plus cabazitaxel or
mitoxantrone for metastatic castration-resistant prostate cancer progressing
after docetaxel treatment: a randomised open-label trial. The Lancet 2010;
376: 1147-1154
8 Scher HI, Fizazi K, Saad F et al.Increased Survival with Enzalutamide in
Prostate Cancer after Chemotherapy N Engl J Med 2012; 367:1187-1197
9 Beer T, Armstrong AJ, Rathkpf D.E et al Enzalutamide in Metastatic
Prostate Cancer before Chemotherapy. N Engl J Med 2014; 371: 424–433.
SACT for Prostate Cancer v2.0
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10 Parker C, Nilsson S, Heinrich D et al. Alpha Emitter Radium-223 and
Survival in Metastatic Prostate Cancer. N Engl J Med. 2013;369(3):213–23.
8.0
CONSULTATION PROCESS
Genito-urinary oncology group.
9.0
APPENDICES / ATTACHMENTS
Authorisation signature sheet.
10.0
EQUALITY STATEMENT
In line with duties under the equality legislation (Section 75 of the Northern
Ireland Act 1998), Targeting Social Need Initiative, Disability discrimination
and the Human Rights Act 1998, an initial screening exercise to ascertain if
this policy should be subject to a full impact assessment has been carried out.
The outcome of the Equality screening for this policy is:
Major impact
Minor impact
No impact.
SACT for Prostate Cancer v2.0
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