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Managing Advanced Prostate
Cancer with ViadurTM (Leuprolide
Acetate Implant)
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Judd W. Moul
Karen Civitelli
C
urrent advanced prostate cancer therapies
are aimed at relieving
symptoms and increasing life expectancy. Prostatectomy, external beam radiation
therapy, and brachytherapy are
generally used to treat localized
prostate cancer. Hormone therapy, used primarily to relieve
symptoms, is the mainstay for
advanced disease because of the
hormone-dependent nature of
prostate cancer cells (Huggins &
Hodges, 1941). The development
of prostate-specific antigen
(PSA) based screening and
increased public awareness precipitated a stage-migration in
detecting prostate cancer such
that fewer patients present with
traditional advanced prostate
cancer. At the same time, the
Judd W. Moul, MD, FACS, is Director,
Department of Defense Center for
Prostate Disease Research, Uniformed
Services University, Rockville, MD.
Karen Civitelli, RN, is Clinical
Research Coordinator, The Urologic
Research Center, The Washington
University School of Medicine, St.
Louis, MO.
Acknowlegment: The authors thank
Dianne Barry, PhD., for expert editorial
assistance.
Note: The opinions and assertions contained herein are the private views of
the authors and are not to be construed
as reflecting the views of the U.S. Army
or the Department of Defense.
ViadurTM (leuprolide acetate implant), providing a sustained release of
drug over a 12- month duration, decreases serum testosterone in
advanced prostate cancer patients, providing long-term, palliative
medical hormonal therapy. Clinical experience suggests Viadur
implants are safe, effective, and generally well tolerated. The continuous drug delivery provided by Viadur ensures compliance. The Viadur
implant was designed to be maintenance-free, thereby allowing nurses
and other health professionals to focus on other patient needs, such
as followup visits and diagnostic tests. Viadur is one aspect of a comprehensive approach to patient management, which also includes regular followup for prostate-specific antigen testing, digital rectal examination, and other tests throughout the 1-year therapy.
Objectives
This educational activity is designed for nurses and other health
care professionals who care for and educate patients regarding
advanced prostate cancer. The multiple choice examination that follows is designed to test your achievement of the following educational
objectives. After studying this offering, you will be able to:
1. Describe the procedure for a Viadur implant.
2. Create a plan of care for the patient with a Viadur implant.
definition of advanced prostate
cancer has broadened (Moul,
1998a). Locally advanced prostate cancer is considered advanced and is treated with longterm adjuvant hormonal therapy
with radiation (Bolla et al., 1997).
Men who have a PSA-based
relapse after surgery or radiation
therapy are now considered
advanced and are candidates for
hormone therapy.
The male androgen testosterone is a mitogenic factor that
contributes to tumor cell proliferation in the prostate (Cook &
Sheridan, 2000; Huggins &
Hodges, 1941). The testes produce approximately 95% of circulating androgens and the
UROLOGIC NURSING / December 2001 / Volume 21 Number 6
remaining 5% are produced by
the adrenal glands. Hormonal
therapy significantly reduces
serum testosterone levels, resulting in diminished tumor size
(Auclerc et al., 2000; Moul,
1998a). At present, hormone therapy is achieved surgically by
orchiectomy or medically by
administration of estrogens,
antiandrogens, or luteinizing hormone-releasing hormone (LHRH)
agonists. These therapies reduce
serum testosterone levels and provide subjective improvement in
about 80% of patients with
metastatic prostate cancer (Moul,
1998a & b).
LHRH agonists mimic the
action of natural LHRH, causing
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Figure 1.
Mean (+ SD) Serum Testosterone Concentrations Measured
from Patients Who Received One Viadur Implant (N=107)
During the 12-month Treatment Phase. No Increased Levels
of Serum Testosterone Were Observed Following
Reimplantation at 52 Weeks.
for palliative treatment of
advanced prostate cancer in the
United States. These agents are as
effective as orchiectomy in
decreasing the level of circulating testosterone (Moul, 1998a).
ViadurTM (leuprolide acetate
implant)
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Figure 2.
Schematic of a Viadur Implant
an initial increase in luteinizing
hormone (LH) secretion from the
anterior pituitary, which stimulates testosterone production by
the testes (Cook & Sheridan,
2000). However, continuous
administration of the drug results
in the desensitization of the pituitary LHRH receptors within a few
days, resulting in a profound
decrease in LH release and consequent suppression of gonadal
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testosterone (Bhasin & Swerdloff,
1986; Kuret & Murad, 1990;
Schally et al., 1989; Schally &
Comaru-Schally, 1997). Reduction
of serum testosterone to castrate
levels is achieved in about 2 to 4
weeks (Hanks, Myers, & Scardino,
1993). In contrast to orchiectomy,
testosterone levels can be reversed
by discontinuing agonist therapy.
Leuprolide acetate and goserelin,
two LHRH agonists, are approved
LHRH agonists were originally formulated for daily subcutaneous administration. To increase
patient compliance, depot LHRH
agonist formulations were developed (Dijkman et al., 1995;
Murphy et al., 1987; Sharifi,
Soloway, and the Leuprolide
Study Group, 1990; Sharifi et al.,
1996; Sharifi, Knoll, Smith, &
Kramolowsky, 1998). However, in
certain populations, particularly
indigent patients, compliance has
been a concern with LHRH agonist therapy (Shaheen, Amin, &
Harty, 1993). Therefore, research
efforts have focused on developing longer-acting formulations to
encourage compliance.
Among the results of this
research has been an implantable
leuprolide
acetate
system,
ViadurTM, a trademark of ALZA
Corporation under license to
Bayer Corporation, that provides
continuous delivery of leuprolide
acetate for 1 year and effective
suppression of serum testosterone
during this period (see Figure 1).
The Viadur implant consists of a
small cylindrical titanium drug
reservoir that is capped by a semipermeable membrane at one end
and a drug-flow moderator at the
other end (see Figure 2). Two
osmotic tablets are adjacent to the
membrane, and a sliding piston
separates the tablets from the
drug. After implanting the device
subcutaneously, water from the
surrounding tissue is drawn
through the membrane causing
the osmotic tablets to swell and
thereby exerting pressure on the
piston. The piston is consequently pushed down, forcing drug into
the subcutaneous tissue at a rate
equal to that of the water entering
the other end of the system.
UROLOGIC NURSING / December 2001 / Volume 21 Number 6
Administration. Insertion
and removal of the Viadur
implant can be performed in an
outpatient setting. While the
patient is lying on his back, his
nondominant arm is flexed at the
elbow, and his hand is positioned out to the side. The site of
insertion in the upper arm is
anesthetized, and, using sterile
technique, a small incision is
made through the skin approximately 8 to 10 centimeters above
the elbow crease in the fossa
between the biceps and the triceps. The implant is inserted
subcutaneously through the incision using a sterile implanter.
The incision site is closed with a
sterile wound closure strip and
covered with a sterile bandage.
To facilitate future removal of the
implant, the location of implant
placement should be carefully
noted with a drawing in the
patient’s chart.
At the completion of the 12month therapy, the device must
be removed and a new Viadur
implant can be inserted. The
implant is located by palpating
the upper-arm area. Once found,
the tissue must be anesthetized
prior to removal. If a new Viadur
implant will be inserted, then the
tissue along the entire path of the
implant should be anesthetized.
However, if the procedure is simply to remove the old implant,
then only the tissue at the distal
end of the implant requires anesthesia. Pressure is applied to one
end of the implant to elevate the
other end for better visibility,
and, using sterile technique, a 4
to 5 millimeter incision is made
at the elevated end of the
implant. By applying gentle pressure, the end of the implant will
emerge from the incision site. If
necessary, the scalpel can be
used to nick any fibrotic encapsulation to free the implant, and
a curved mosquito clamp can be
used to facilitate expulsion.
After insertion or removal,
the patient must be observed for
signs of bleeding from the inci-
sion site before discharge.
Patients must be instructed to
keep the area clean and dry for 24
hours and to avoid strenuous
physical activity for 48 hours.
The wound closure strip can be
removed in about 3 days, after
the incision has sealed.
Side effects. Possible complications of inserting the implant
include infection, reactions to
the dressing, and expulsion of
the implant, all of which are relatively rare. Most patients experience some transient bruising and
edema, whereas local allergic
reactions are rare. Patients
should be advised that any application-site reactions that occur
are likely to be mild and might
require minimal intervention
such as an over-the-counter analgesic. The patient should be
aware of signs and symptoms of
infection and instructed to contact his physician assistant or
physician promptly should they
occur. It should be noted that
Viadur was not studied in
women or children and is contraindicated in female and pediatric patients. In addition, Viadur
is contraindicated for patients
with hypersensitivity to GnRH,
GnRH agonist analogues, as anaphylactic reactions to synthetic
GnRH or GnRH agonist analogs
have been reported (MacLeod,
Eisen, & Sussman, 1987).
Potential side effects of
androgen deprivation, particularly hot flashes and sexual dysfunction, should be discussed,
and patients should be informed
about measures that can be
employed to alleviate these problems if they become too distressing. Viadur, like other LHRH agonists, causes a transient increase
in serum concentrations of
testosterone during the first week
of treatment. Patients may experience worsening of symptoms or
onset of new symptoms, including bone pain, neuropathy,
hematuria, or ureteral or bladder
outlet obstruction. Cases of
ureteral obstruction and spinal
UROLOGIC NURSING / December 2001 / Volume 21 Number 6
cord compression, which may
contribute to paralysis with or
without fatal complications,
have been reported with LHRH
agonists. If spinal cord compression or renal impairment develops, standard treatment of these
complications should be instituted. Several interventions for side
effects related to Viadur implant
therapy are presented in Table 1.
Nursing interventions. Thorough patient assessments should
be conducted on a regular basis to
monitor any change in disease
symptoms and drug-related side
effects. Most men with advanced
prostate cancer are seen every 3 to
6 months in followup. Symptom
assessment, physical examination
including DRE, and laboratory
tests such as PSA are obtained.
Testosterone levels should also be
assessed for patients demonstrating an increase in PSA levels. In
addition, patients who are taking
anti-androgens must have periodic measurements of liver enzymes. Complete blood count and
renal function are assessed based
on history and physical examination, or at least annually. Skin
integrity at the insertion site of
the Viadur implant should be
observed and documented. Rare
implant insertion complications
include infection and reactions
to the dressing. Transient bruising and edema often occur after
insertion. Patients should be
advised that any local reactions
that occur are likely to be mild
and transient, and may require
minimal treatment such as an
over-the-counter analgesic. The
patient should also be aware of
signs and symptoms of infection
and instructed to contact his
nurse or physician promptly if
they occur.
Potential side effects of hormone therapy, particularly hot
flashes and sexual dysfunction,
should be discussed, and patients
should be informed about potential interventions to alleviate
these problems if they become too
distressing (see Table 1). Nurses
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Table 1.
Nursing Care Plan for Patients Treated with Viadur Implant
Nursing Diagnosis
Knowledge deficit
regarding treatment
with Viadur implant
Expected Outcome
Nursing Interventions
Patient will verbalize understanding of
treatment plan and the effects of Viadur
implant.
1.
2.
3.
4.
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5.
6.
Anxiety related to
cancer diagnosis and
treatment
Patient will demonstrate effective coping
strategies.
1.
2.
3.
4.
Altered comfort related
to hot flashes
Patient will verbalize feelings regarding
hot flashes and identify coping strategies.
1.
2.
3.
4.
Risk for sexual
dysfunction
Patient or his partner is able to verbalize
concerns about sexual functioning.
1.
2.
3.
4.
5.
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Assess baseline knowledge of disease and treatment strategies.
Explain purpose of drug, potential
side effects, and side effect management.
Explain insertion and removal procedures for the drug implant. Give
information on post-insertion care.
Caution patients against having any
procedures done in the implanted
arm that could displace the implant.
Stress importance of replacing
Viadur implant in 12 months.
Encourage questions.
Assess patient and family member
or caretaker for signs and symptoms of anxiety.
Explore specific factors, which may
be triggering anxiety.
Encourage coping strategies such
as involvement of group support
systems, use of previous coping
strategies, and alternative coping
strategies.
Provide referrals as indicated.
Assess patient for signs and symptoms of flushing.
Discuss effect that hot flashes have
on the patient’s life. If significant,
discuss pharmaceutical options
such as megestrol or estrogen with
physician. Vitamin E or soy supplement may be helpful.
Suggest that avoiding caffeine,
spicy foods, and alcohol may be
helpful.
Advise patient to lower room temperature and wear several layers of
loose-fitting clothes, which can be
removed when a hot flash occurs.
Give patient or partner permission
to express sexual concerns.
Explore current and past sexual patterns and expectations for sexual
function.
Provide privacy and confidentiality
during all conversations.
Educate patient and partner on
basic sexual physiology and effect
of disease and treatment.
Help couple communicate sexual
concerns to each other. Assist in
identifying options to deal with sexual dysfunction, such as alternative
ways to express intimacy.
UROLOGIC NURSING / December 2001 / Volume 21 Number 6
Table 1. (continued)
Nursing Care Plan for Patients Treated with Viadur Implant
Nursing Diagnosis
Expected Outcome
Risk for sexual
dysfunction (continued)
Nursing Interventions
6.
7.
Risk for flare reaction
Patient will identify signs and symptoms
to report to health care provider.
1.
2.
3.
4.
Impaired skin integrity
Patient will identify signs and symptoms
to report to health care provider and
describe measures to protect and heal
incision site.
1.
2.
3.
should review signs and symptoms that may arise as a result of
disease flare, such as new or
increasing bone pain, urinary
obstruction, or parasthesia of the
legs. Patients should be instructed
to promptly notify their nurse or
physician if any of these events
occur; rapid treatment may be
required to prevent or remedy any
serious complications.
Summary
The Viadur implant is an
osmotically driven therapeutic
system for the palliative treatment of advanced prostate cancer. It is designed to deliver a sustained, low dose of leuprolide
acetate at levels necessary to
achieve hormone ablation. Clinical experience suggests that
Viadur is safe, effective, and gen-
UROLOGIC NURSING / December 2001 / Volume 21 Number 6
Discuss therapies available to deal
with erectile dysfunction, such as
drugs and external devices.
Provide professional referrals as
indicated.
Provide ongoing patient assessment.
Closely monitor patients with
metastatic lesions for signs of
spinal cord compression.
Instruct patient to call health care
provider immediately if signs of
tumor progression appear:
• Progressive pain.
• Weakness.
• Motor impairment.
• Autonomic dysfunction.
• Sensory changes.
• Impaired urinary flow or retention.
Document pain, control methods,
and effectiveness.
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Instruct patient on post-discharge
care of implant incision site:
• Temporary or transient bruising,
swelling, and pain may occur.
• Keep site clean and dry for 24
hours.
• Avoid strenuous activity for 48
hours.
• Remove dressing when the incision has sealed, usually in 3 to 4
days.
Teach patient to promptly report
signs and symptoms of infection,
bleeding, or implant expulsion to
the health care provider.
Assess skin integrity on ongoing
basis.
erally well tolerated. Urology
nurses will be responsible for
assisting in the insertion and
removal of Viadur implants, and
educating patients about hormone therapy and the Viadur
implant system. The once-a-year
placement of the Viadur implant
may allow for fewer office visits
and decreased staff time for
administration. However, moni-
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toring patients for emerging drug
side effects and disease symptoms is still necessary. Therefore,
careful assessment and coordination of the patient’s overall treatment plan will be key to maximizing the benefits of therapy. •
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Moul, J.W. (1998b). Contemporary hormonal management of advanced
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(1997). Hypothalamic and other peptide hormones. In J.F. Holland, R.C.
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Additional Reading
Fowler, J.E. Jr., Flanagan, M., Gleason,
D.M., Klimberg, I.W., Gottesman, J.E.,
& Sharifi R. (2000). Evaluation of an
implant that delivers leuprolide for 1
year for the palliative treatment of
prostate cancer. Urology, 55, 639-642.
Fowler J.E. Jr., Gottesman J.E., Reid, C.F.,
Andriole, G.L. Jr., & Soloway, M.S.
(2000). Safety and efficacy of an
implantable leuprolide delivery system in patients with advanced
prostate cancer. Journal of Urology,
164, 730-734.
Garnick, M.B. (1997). Prostate cancer. In
D.D. Federman, & D.C. Dale (Eds.),
Scientific American medicine (pp. 110). New York: Scientific American.
Labrie, F., Dupont, A., Belanger, A. et al.
(1984). Simultaneous administration
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