Intermittent Androgen Deprivation Therapy for Treatment of Prostate Cancer – What are the Benefits? Release Date: 08/05/2011 Expiration Date: 08/05/2014 FACULTY: Juli Aistars, RN, MS, AOCN, APN Prostate Nurse Navigator, Northwest Community Hospital Arlington Heights, IL FACULTY AND ACCREDITOR DISCLOSURE STATEMENTS: Juli Aistars has no actual or potential conflict of interest in relation to this program. ACCREDITATION STATEMENT: Pharmacy PharmCon Inc is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. Program No.: 0798-0000-11-052-H01-P Credits: 1 contact hour, 0.1 CEU Nursing Pharmaceutical Education Consultants, Inc. has been approved as a provider of continuing education for nurses by the Maryland Nurses Association which is accredited as an approver of continuing education in nursing by the American Nurses Credentialing Center’s Commission on Accreditation. Program No.: N-682 Credits: 1 contact hour, 0.1 CEU
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Intermittent Androgen Deprivation Therapy for Treatment of Prostate Cancer – What are the Benefits?
Release Date: 08/05/2011
Expiration Date: 08/05/2014
FACULTY:
Juli Aistars, RN, MS, AOCN, APN Prostate Nurse Navigator, Northwest Community Hospital Arlington Heights, IL
FACULTY AND ACCREDITOR DISCLOSURE STATEMENTS:
Juli Aistars has no actual or potential conflict of interest in relation to this program.
ACCREDITATION STATEMENT:
Pharmacy PharmCon Inc is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. Program No.: 0798-0000-11-052-H01-P Credits: 1 contact hour, 0.1 CEU
Nursing
Pharmaceutical Education Consultants, Inc. has been approved as a provider
of continuing education for nurses by the Maryland Nurses Association which is
accredited as an approver of continuing education in nursing by the American
Nurses Credentialing Center’s Commission on Accreditation.
Program No.: N-682
Credits: 1 contact hour, 0.1 CEU
TARGET AUDIENCE:
This accredited program is targeted to pharmacists and nurses practicing in hospital and community pharmacies. Estimated time to complete this monograph and posttest is 60 minutes.
DISCLAIMER:
PharmCon, Inc does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced and objective. Occasionally, authors may express opinions that represent their own viewpoint. Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient or pharmacy management. Conclusions drawn by participants should be derived from objective analysis of scientific data presented from this monograph and other unrelated sources.
Program Overview:
To provide Pharmacists and Nurses with an understanding of Androgen Therapy and its relation to Prostate Cancer treatment.
OBJECTIVES:
After completing this program, participants will be able to:
1. Review the etiology and epidemiology of prostate cancer.
2. Outline the types of androgen deprivation therapy
3. Describe androgen deprivation therapy to include mechanism of action, side
effects and means to mitigate the side effects
Aistars – Androgen Therapy Page 1
Intermittent Androgen Deprivation Therapy for Treatment of Prostate Cancer –
What are the Benefits?
Juli Aistars, RN, MS, AOCN, APN
Prostate Nurse Navigator, Northwest Community Hospital
Arlington Heights, IL
Mr. Q is a 74 year old man with a history of prostate cancer diagnosed 2 years ago after his PSA
increased from 5.67 to 11.6 over one year. It was high-grade with a Gleason of 5+4 present in
both lobes and with extracapsular extension (locally advanced). He has a history of coronary
artery disease and atrial fibrillation. After a bone and CT scan were negative for metastases, he
received intensity modulated radiation therapy to the prostate, seminal vesicles and adjacent
pelvic nodes. He was also started on post-radiation androgen deprivation therapy (ADT). He was
exercising daily before treatment but has decreased that to two days a week because of the
fatigue. He experienced the side effects of fatigue, weight-gain, hot flashes, and decreased libido
from ADT. He had done his own research and wanted to know if he was a candidate for
intermittent ADT to decrease side effects and decrease his out-of-pocket cost. He had missed his
last ADT injection because he was considering stopping it altogether because of how it was
affecting his life. In this paper, the questions below will be addressed and related specifically to
Mr. Q’s situation.
1. What are the indications for ADT in prostate cancer?
2. What are the possible side effects of ADT?
3. Can side effects be mitigated with intermittent androgen deprivation therapy (IAD)?
4. Is adherence to ADT increased with IAD?
5. Is long-term survival compromised with IAD?
Introduction
About 230,890 new cases of prostate cancer will occur in the US alone during 2011. The number
of deaths predicted in 2011 is 33,720, making it the second leading cause of cancer death in men.
Besides skin cancer, it is the most frequently diagnosed cancer in men.1
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Because prostate cancer is being detected earlier with the advent of the PSA test in the 1990s,
more men are surviving prostate cancer. In North America, there are approximately 2 million
men who are surviving after a diagnosis of prostate cancer. Of these, 700,000 are either
chemically or surgically castrated (suppression of testosterone). At the current rate of detection
of prostate cancer, it is possible that as many as 4% of Caucasian men may eventually be treated
with chemical or surgical castration.2 The focus on quality of life in these men is becoming
increasingly more important, since they may be living with the side effects for many years.
Surgical castration is removal of the testicles to interrupt the production of testosterone.
Chemical castration, which is the focus of this paper, is accomplished by various forms of
androgen deprivation therapy. This treatment can be used continuously or intermittently (on-
again, off-again). The idea behind intermittent therapy is the potential for delaying progression to
androgen independence (hormone resistant prostate cancer), as well as improving quality of life.
There is some evidence that Intermittent Androgen Therapy can reverse anemia and also reduce
the risk of diabetes and cardiovascular disease caused by continuous androgen deprivation
therapy.3
Definition of Androgen Deprivation Therapy (ADT)
Prostate cancer growth is dependent on androgens (male hormones). In men, androgens are
produced by the testes and by the adrenal glands. The testes are the main source of testosterone,
while the rest of the androgens produced by the adrenal glands are precursors that are converted
to testosterone and dihydrotestosterone in prostatic and peripheral tissues. Hormone therapy for
prostate cancer does not mean adding hormones but depriving the cancer of androgens so that
growth of the cancer is slowed down.4
Mechanism of Action
There are various means of chemical castration, the most common being suppression of the
release of luteinizing hormone from the anterior pituitary. Other hormonal interventions for
Aistars – Androgen Therapy Page 3
prostate cancer cause depletion of androgens by inhibition of adrenal androgen synthesis. The
mechanism for suppression is by direct inhibition of the androgen receptor, 5 alpha reductase,
which converts testosterone to dihydrotestosterone (DHT).
Indication for ADT in Prostate Cancer
ADT, either surgical or medical, is the frontline treatment for advanced prostate cancer to slow
down the spread of cancer cells to distant sites (secondary or adjuvant therapy). It can be carried
out by surgical or medical castration as outlined above. Medical ADT may be used in localized
prostate cancer to shrink the prostate and the tumor before a procedure to reduce the likelihood
of spread or as an adjunct to radiation therapy for high-risk localized disease (neoadjuvant
therapy) and to ease pain caused by the spread of cancer (palliative). Of the 2 million men with
prostate cancer in the United States, over one-third have received ADT treatment.5
Types of ADT6
Surgical castration
Orchiectomy – surgical removal of the testicles, where more than 90% of the androgens,
mostly testosterone, are produced. Most prostate cancers will stop growing and shrink
once the source of androgens is removed. An orchiectomy is an outpatient procedure and
is the least expensive type of ADT. The disadvantage is that it is permanent, and it is
psychologically difficult for most men.
Chemical castration
Luteinizing hormone-releasing hormone (LHRH) analogs, also called LHRH agonists or
GnRH agonistsThese agents are expensive and require more frequent physician visits.
The advantage is that the testicles will remain in place, although they will shrink over
time. These agents interfere with the release of follicle-stimulating and luteinizing
Aistars – Androgen Therapy Page 4
hormone from the pituitary gland and reduce the production of testosterone from the
testes.
LHRH analogs are injected or placed as small implants under the skin. They can be given
from once a month up to once a year. The agents available in the U.S. are leuprolide
(Lupron®, Viadur®, Eligard®), goserelin (Zoladex®), triptorelin (Trelstar®), and
histrelin (Vantas®). When treatment is started, testosterone production increases or flares
briefly before falling to low levels. This effect is called a tumor flare. It can cause
complications like increased bone pain or spinal compression, depending on if bone
metastases are present. Flare can be mitigated with drugs called anti-androgens given for
a few weeks when starting treatment with LHRH analogs.