Docetaxel Use in Prostate Cancer

Randy A. Jones, PhD, APRNAssistant Professor

University of Virginia School of Nursing

Charlottesville, Virginia

What Is Docetaxel?

• The only US FDA approved chemotherapeutic agent for clinical treatment of advanced hormone refractory prostate cancer

• A chemotherapy drug that treats cancer (eg, breast, non–small-cell non–small cell lung and prostate cancer)

FDA = Food and Drug Administration.Pazdur R and Keegan P. FDA Approval for Docetaxel. Cancer Website. Available at: http://www.cancer.gov/cancertopics/druginfo/fda-docetaxel#Anchor-Prostat-16229. Accessed December 31, 2007.

Drug Type of Therapy Phase Trial Overview Goals

Bevacizumab Anti-angiogenic III CALGB 90401:docetaxel/ prednisone + bevacizumab

• Eliminate/preventsymptoms

• Delay progression

Atrasentan Endothelin-1

receptor antagonist

III SWOG 04-21:docetaxel and atrasentan vs docetaxeland placebo for patients

• Delay progression• Eliminate/prevent

symptoms

Prostate GVAX Vaccine III Vital 1:GVAX® vs docetaxel + prednisone

Vital 2:docetaxel + GVAX® + prednisone vs. docetaxel + prednisone

• Delay progression

DN-101 Vitamin D receptor (Trial ended Nov 2007 for an imbalance of deaths between 2 treatment arms)

III ASCENT 2: docetaxel + prednisone + DN-101

• Effects on skeletal related events

Investigational Phase III Trials with Docetaxel

AIPC = androgen-independent prostate cancer; ASCENT = AIPC Study of Calcitriol Enhancing Taxotere; CALGB = Cancer and Leukemia Group B; DN = high-dose calcitriol; GVAX = Gene-Transduced Irradiated Prostate Allogeneic Cancer Cell Vaccines SWOG = Southwest Oncology Group.Di Lorenzo G. Drugs. 2007; 67:1109-1124; and Mendiratta P. Rev Urol. 2007;9:S9-S19 .

Administration of Docetaxel

• Docetaxel is available in 20-mg (0.5 mL) or 80-mg (2 mL) vials and requires dilution prior to use

• The diluent contains 13% ethanol in water for injection

• Docetaxel is infused through the vein for approximately 1 hour every 3 weeks

Dose of Docetaxel

• 75 mg/m2 IV every 3 weeks for 10 cycles• Give with 5 mg oral prednisone twice daily throughout

treatment• throughout treatment• Premedicate with dexamethasone

– Decrease or delay incidence of fluid retention and allergic reactions1

– Pretreatment regimen for hormone refractory prostate cancer is 8 mg dexamethasone at 12 hours, 3 hours,1 2 hours, and 1 hour before docetaxel infusion2

• Docetaxel + prednisone given when neutrophil count is >1500 cells/mm3

IV = intravenous.1. Piccart, M. J Clin Onc. 1997;15:3149-3155.2. Dagher R, Li N, et al. Clin Cancer Research. 2004;10:8147-8151.

Docetaxel Dosage to Manage Adverse Events

Response Condition

Reduce docetaxel to 60 mg/m2 if: • Febrile neutropenia• Prolonged neutropenia• Neutropenic infection• Severe cutaneous reactions• Moderate neurosensory signs and/or

symptoms

If adverse reactions continue: • Discontinue treatment

Do not administer, or discontinue use of docetaxel if:

• Neutrophil count <1500 cells/mm3

Dagher R et al. Clin Cancer Res. 2004;10:8147-8151.

Safety and Efficacy

• Treatment of metastatic prostate cancer is palliative

• Two phase 3 trials (TAX 327 and SWOG 9916) have shown improved 2 phase 3 trials (TAX 327 and SWOG 9916) have shown improved survival rate when using docetaxel– TAX 327 compared men who received Docetaxel every 3 weeks or

weekly, men who received docetaxel every 3 weeks or weekly, with men who received mitoxantrone every 3 weeks. The docetaxel every 3

weeks arm had a median survival of 18.9 months vs versus 16.5 months in the mitoxantrone arm (P = .009)

– SWOG 9916 compared docetaxel plus estramustine and mitoxantrone plus prednisone; median survival was 17.5 months for the docetaxel arm and 15.6 months among the mitoxantrone arm (P = .02). ; median survival was 17.5 months for the docetaxel arm and 15.6 months among the mitoxantrone arm (P = 0.02)

Petrylak D et al. N Engl J Med. 2004;351:1513-1520.Tannock I, et al. N Engl J Med. 2004;351:1502-1512.

Maximize Benefits of Chemotherapy

• Be aware of adverse effects and anticipate treatment as needed– Minimize nausea– Adjust to hair loss– Minimize fatigue– Be aware of peripheral neuropathy – Help patient establish a support network

Potential Adverse Effects of Docetaxel

• Leukopenia• Potential for fluid retention• Nausea and vomiting• Hair loss• Peripheral neuropathy• Diarrhea (drink plenty of fluids)• Fatigue (potentially from anemia)

Adverse Effect: Leukopenia

• Routine blood draws are taken to identify if WBC counts are low

• Potential increased risk for infection• Monitor for fever

WBC = white blood cells

Adverse Effect:Fluid Retention

• Medications

– Dexamethasone (corticosteroid) has been

seen to delay the onset of fluid retention by

decreasing potential inflammation

Piccart M. J Clin Oncol. 1997;15:3149-3155.

Adverse Effect:Nausea and Vomiting

• Eat small portions of food throughout day• Eat dry foods (eg, crackers or toast)• Avoid high-fat or greasy foods• Suck on ice chips or hard candy• Medications – Dexamethasone in combination with ondansetron

Adverse Effect:Hair Loss

• Usually temporary• Comb or brush hair gently• Use mild shampoo• Place sunscreen on scalp• Wear a hat when outside in the sun

Adverse Effect: Peripheral Neuropathy

• Patient education includes:– Be aware of thermal injury

– Wear shoes to promote foot care

– Examine bottom of feet daily

– Report signs and symptoms of peripheral neuropathy to a healthcare provider

Visovsky C et al. Clin J Oncol Nurs. 2007;11:901-913.

Adverse Effect:Fatigue

• Take scheduled rest breaks

• Join a support group

• Ask for help to accomplish activities

• Exercise– Keep muscles conditioned

– 2-site study examined resistance exercise program with a control and found men assigned to resistance exercise had less fatigue and higher quality of life than control group.* 2-site study examined resistance exercise program with a control and found men assigned to resistance exercise had less fatigue and higher quality of life than the control group

Segal R. J Clin Oncol. 2003;21:1653-1659.

Help Establish Support Network

• Help patients identify trusting individuals to whom they can speak openly about their disease

• Offer a listing of surrounding support groups and resources

• Involve family members and/or friends when appropriate

Other Potential Adverse Effects

• Patient may be receiving hormone therapy– May experience sexual dysfunction

• Suggest medication (eg, sildenafil, tadalafil, and vardenafil)• Suggest open discussion with sexual partner

to plan how to fulfill sexual desires

– May experience hot flashes• Recommend comfort measures—cold/warm towels (taking

in consideration for avoidance of potential thermal injury) (taking into consideration for avoidance of potential thermal injury)

• Possibly prescribe medications (ie, gabapentin)

Nursing Strategies to Prevent, Identify, and Manage Adverse Effects

• Assist patient to schedule uninterrupted quiet/rest times

• Provide comfort measures• Provide patient- and family-centered care• Provide education to patient and family• Be aware of patient’s concerns about

treatment/adverse effects• Develop a plan of care and evaluate its

effectiveness