Treatment of Hormone-refractory Prostate Cancer

2. 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

3. 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.

4. 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.

5. Docetaxel Schedules and Toxicities in Hormone-refractory Prostate Cancer *In combination with prednisone; both regimens tested against mitoxantrone. Tannock IF et al. N Engl J Med. 2004;351:1502-1512.

6. 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.

7. 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

8. 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)

10. 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.

11. Common Agents for Prevention of Hypersensitivity With Taxanes 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.

12. 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.

13. 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 10-mL 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.

14. 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.

15. 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