Transcript Docetaxel Use in Prostate Cancer

Docetaxel Use
in Prostate Cancer
Randy A. Jones, PhD, APRN
Assistant 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/fdadocetaxel#Anchor-Prostat-16229. Accessed December 31, 2007.
Investigational Phase III Trials
with Docetaxel
Drug
Type of Therapy
Phase
Trial Overview
Goals
Bevacizumab
Anti-angiogenic
III
CALGB 90401:
docetaxel/ prednisone + bevacizumab
• Eliminate/prevent
symptoms
• Delay progression
Atrasentan
Endothelin-1
receptor antagonist
III
SWOG 04-21:
docetaxel and atrasentan vs docetaxel
and placebo for patients
• Delay progression
• Eliminate/prevent
symptoms
Prostate GVAX
Vaccine
III
Vital 1:
GVAX® vs docetaxel + prednisone
• Delay progression
Vital 2:
docetaxel + GVAX® + prednisone vs.
docetaxel + prednisone
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
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 80mg (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:
•
•
•
•
•
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.
Febrile neutropenia
Prolonged neutropenia
Neutropenic infection
Severe cutaneous reactions
Moderate neurosensory signs and/or
symptoms
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