Treatment of Hormone-refractory
Prostate Cancer
Sandra Kurtin, RN, MS, AOCN, ANP-C
Hematology/Oncology Nurse Practitioner

Arizona Cancer Center
Clinical Assistant Professor of Nursing
Clinical Assistant Professor of Medicine
University of Arizona
Tucson, AZ
NCCN Guidelines: Treatment
of Hormone-refractory
Prostate Cancer
• Docetaxel-based regimens have been shown to confer survival
benefit in two phase 3 studies
• SWOG 9916 compared docetaxel plus estramustine with
mitoxantrone plus prednisone; median survival for the
docetaxel arm was 18 months vs 15 months for the
mitoxantrone arm (P = .01)
• TAX 327 compared 2 docetaxel schedules (weekly and every 3
weeks) with mitoxantrone and prednisone; median survival for
the every-3-weeks docetaxel arm was 18.9 months vs 16.5
months for the mitoxantrone arm (P = .009)
• Mitoxantrone with prednisone has been shown to provide
palliative benefit in patients with painful bony metastases from
castration-recurrent prostate cancer; however, its efficacy as
second-line therapy after docetaxel has not been determined
National Comprehensive Cancer Network (NCCN) Practice Guidelines in Oncology , v2, 2007.
http://www.nccn.org/professionals/physician_gls/PDF/prostate.pdf.
NCCN Guidelines:
Treatment of Hormone-refractory
Prostate Cancer (cont’d)
• Docetaxel-based regimens are now the
standard of care for first-line treatment in this
group of patients
• The US Food and Drug Administration has
approved docetaxel for injection in
combination with prednisone for the
treatment of castration-recurrent metastatic
(hormone-refractory, androgen-independent)
prostate cancer
NCCN Practice Guidelines in Oncology , v2, 2007. http://www.nccn.org/professionals/physician_gls/PDF/prostate.pdf.
Docetaxel Schedules and Toxicities in
Hormone-refractory Prostate Cancer
Docetaxel*
30 mg/m2 weekly
(n = 330)
Docetaxel*
100 mg/m2
every 3 weeks
(n = 332)
Neutropenia (≥ grade 3)
2%
32%
Anemia (≥ grade 3)
5%
5%
Neuropathy
24%
30%
Fatigue
49%
53%
Nail changes
37%
30%
Tearing
21%
10%
Stomatitis
17%
20%
Adverse Event
(% of patients)
*In combination with prednisone; both regimens tested against mitoxantrone.
Tannock IF et al. N Engl J Med. 2004;351:1502-1512.
Taxane-associated Hypersensitivity
• Incidence: ≈40% of all patients experience minor
reactions (≈3% life-threatening) despite
premedications
• Overall incidence
• Paclitaxel: 8% to 45%
• Docetaxel: 5% to 20%
• Onset: Immediate to within 5–10 minutes
• Signs and symptoms: “feeling funny”, flushing,
lightheadedness, pruritus, back pain, tightness
in chest/neck, bronchospasm, angioedema,
hypotension, hypertension
Lenz HJ. Oncologist. 2007;12:601-609.
Hypersensitivity Reactions in the
Outpatient Oncology Setting
• Virtually all chemotherapeutic agents have
the potential to initiate a hypersensitivity
reaction
• Reactions often happen in a matter of
seconds and without cutaneous symptoms
• Anaphylaxis occurs as a continuum
• Symptoms are not immediately life-threatening but
may progress rapidly if not treated promptly
Clinical Dilemma:
Balancing the Risk and Benefit
• Discontinuation or delay of potentially
curative therapy
• Delivery of substandard therapy
• Patient safety is the primary concern
• Death most commonly results from
intractable bronchospasm, asphyxiation
from upper airway edema, or
cardiovascular collapse (vascular leak)
Prevention Is the Best Strategy
•
Know the patient
• Primary diagnosis: bulky disease, pulmonary disease, neuroendocrine
tumors, carcinoid
• Comorbidities: congestive heart failure, reactive airways disease,
chronic obstructive pulmonary disease (COPD), diabetes, atrial
fibrillation, hepatic
or renal disease (decreased metabolism/excretion)
• Concomitant mediations: prednisone, cardiac medications
• Previous treatment: increased risk for reactions
• History of hypersensitivity to medications
•
Know the drug
• Risk is increased with higher doses, rapid infusion rate, drugs derived
from bacteria (L-asparaginase) or given as crude preparations (phase I
drugs), monoclonal antibodies, taxanes, and platinum compounds
•
Know the interventions
• Adopt a protocol for management of anaphylactoid/anaphylactic
reactions
Khoukaz T. Semin Oncol Nurs. 2006;22:20-27.
Common Agents for Prevention
of Hypersensitivity With Taxanes
Class
Agents and Dosing
H1 antagonist
Diphenhydramine 50 mg IV
H2 antagonist
Cimetidine 300 mg IV 30 min prior
Ranitidine 50 mg IV 30 min prior
Famotidine 20 mg IV 30 min prior
Steroid
Paclitaxel:
Dexamethasone 20 mg IV 30 min prior
or 8–20 mg orally 12 and 6 h prior
Docetaxel:
Every 3 weeks: 8 mg (orally 1 day prior, twice daily  3
days)
Weekly: 4–8 mg (1 h prior)
For prostate cancer: dexamethasone 8mg PO 12, 6 and 1
hour prior to infusion.
Hainsworth JD. Oncologist. 2004;9:538-545; Kwon JS et al. Gynecol Oncol. 2002;84:420-425; Markman M et al. J Cancer Res Clin Oncol.
1999;125:427-429.
Treatment of Hypersensitivity
• Patient exhibits signs and symptoms of hypersensitivity
• Stop infusion
• Institute ABCs—airway, breathing, circulation
• Assess—vital signs, pulse oximeter, patient complaints
• Notify provider
• If mild to moderate
• Treat symptoms
• Provide ongoing assessment until provider arrives
• Administer additional premedications if indicated
• Consider rechallenging the patient with a 50% reduction in
infusion rate with gradual titration as tolerated
• Monitor closely during infusion and for 1 hour following
infusion
• Premedicate for future infusions and consider steroid taper
Khoukaz T. Semin Oncol Nurs. 2006;22:20-27.
Treatment of Hypersensitivity (cont’d)
•
If moderate to severe with airway symptoms
• Initiate emergency services based on institution policy
• Administer diphenhydramine 25–50 mg IV, hydrocortisone 100
mg IV
• If patient exhibits progressive symptoms with airway
compromise
• Give epinephrine (1:1000) 0.3–0.5 mL subcutaneous, repeat
every 5–15 minutes
• If no improvement, give epinephrine (1:10,000 solution in 10mL syringe) 1 mg over 5 minutes, maximum of 3 doses
• Patient will require monitoring overnight
• If continued airway symptoms, 2 puffs albuterol metered-dose
inhaler
• If O2 saturation <90%, administer 100% O2, use nonrebreather
for patients with COPD/CO2 retention
Khoukaz T. Semin Oncol Nurs. 2006;22:20-27.
Steroid-induced Hyperglycemia
in the Cancer Patient
• Steroids induce a state of relative insulin resistance
• May promote glucose production in the liver
• Reduce binding of insulin to the insulin receptor on cells
• Decrease insulin secretion from the islet cell
• Insulin resistance causes primarily postprandial
hyperglycemia
• Patients with cancer who are receiving steroids as a part of
their therapy may develop treatment-related hyperglycemia
or overt diabetes
• Patients with existing diabetes may require modification of
their diabetes medication regimen
• Steroid-induced diabetes is related to the dose of steroids
used but not the type
Oyer DS et al. J Support Oncol. 2006;4:479–483.
Steroid-induced Hyperglycemia
in the Cancer Patient (cont’d)
• Common symptoms associated with
hyperglycemia
• Polydipsia (excessive thirst)
• Polyphagia (excessive hunger)
• Polyuria (excessive urination)
• Agitation, irritability
• Fatigue
• Nausea, vomiting
• Dry mouth
• Visual disturbances