A Randomised Double-Blind Placebo Controlled Cross Over Trial of the Impact on Quality of Life of Continuing Dexamethasone Beyond 24 Hours Following Moderately Emetogenic Chemotherapy
18 Years
N/A
Female
Cancer, Emesis, Nausea
Trial Information
A Randomised Double-Blind Placebo Controlled Cross Over Trial of the Impact on Quality of Life of Continuing Dexamethasone Beyond 24 Hours Following Moderately Emetogenic Chemotherapy
Background: Dexamethasone improves control of acute nausea and vomiting when given prior to
chemotherapy, and continued administration of dexamethasone improves nausea and vomiting
after highly emetogenic chemotherapy. There is no consensus about the optimal regimen for
control of delayed emesis after moderately emetogenic chemotherapy but most patients receive
oral dexamethasone. Many patients complain of insomnia, anxiety/agitation and indigestion
whilst they are on dexamethasone, and fatigue and depressed mood after stopping it. The
impact of these symptoms on patients has not been studied systematically. While patients
with less vomiting and nausea are expected to have better quality of life (QOL), the QOL of
patients with minimal nausea or vomiting might be more affected by the side effects of
antiemetic treatment.
Hypothesis: Dexamethasone given as an antiemetic for delayed nausea and vomiting after
moderately emetogenic chemotherapy reduces overall quality of life.
Research Question: Does the use of dexamethasone as a prophylactic antiemetic for delayed
nausea and vomiting following moderately emetogenic chemotherapy decrease overall quality of
life, as evaluated by the European Organisation for Research and Treatment of Cancer Quality
of Life Questionnaire (EORTC QLQ C-30).
Study Design: Using a double-blind randomised cross-over design, we will determine:
- (i) the effect of oral dexamethasone (4mg PO bid after chemotherapy) versus an
identical appearing placebo on QOL of patients that receive moderately emetogenic
chemotherapy, and
- (ii) patient preference for dexamethasone or placebo.
We will evaluate control of nausea and vomiting and the impact of both the side effects of
dexamethasone and of nausea and vomiting on QOL. Therapy for acute emesis will be
standardised (single dose intravenous granisetron and dexamethasone) and all patients will
receive granisetron for delayed emetic control. Each patient will be randomly allocated to
receive either dexamethasone or placebo after the first cycle of chemotherapy, and crossed
over to the other arm for the second cycle. Patients will complete questionnaires that
evaluate QOL, symptoms associated with dexamethasone, and nausea and vomiting at baseline
and one week after their intravenous chemotherapy; they will also record symptoms in a daily
diary.
The primary outcome measures are patient preference and overall QOL. The secondary
objectives are: (1) to compare complete protection from delayed vomiting and severity of
nausea between those receiving dexamethasone and those receiving placebo; (2) to compare
differences in the impact of nausea and vomiting on QOL in those receiving dexamethasone and
those receiving placebo, and (3) to compare differences in symptoms that have been
associated with dexamethasone (insomnia, anxiety, agitation, mood, etc.) between patients
receiving dexamethasone and those receiving placebo.
Significance: Our study will evaluate whether the benefits of dexamethasone for delayed
emetic control outweigh potential side effects in patients receiving moderately emetogenic
chemotherapy. It addresses a problem that is important to the majority of patients receiving
anticancer chemotherapy. If overall QOL is improved on dexamethasone, then it should be
prescribed routinely. If QOL is reduced on dexamethasone, and patients prefer the placebo,
then its use as an antiemetic after moderately emetogenic chemotherapy should be limited to
patients who initially have poor control of emesis.
Inclusion Criteria:
- Patients diagnosed with breast cancer who will receive their first cycle of
non-cisplatin moderately emetogenic chemotherapy. The following regimens can be
administered:
- 14-day regimens dose dense
- 21-day regimens:
- Adriamycin and Cyclophosphamide (AC) + a Taxane (T) Other regimens are
eligible as long as no cisplatin or other highly emetogenic agent is part
of the regimen, and a moderately emetogenic agent is included.
- Aged > 18 years
- Performance status of 0-2 on the European Cooperative Oncology Group (ECOG)
performance scale
- Full recovery from any post operative sequelae
- Patients on opioids are eligible as long as their doses are stable (no change to dose
in the previous week) and they have no nausea or vomiting in the 24 hours prior to
the study
- Informed signed consent
Exclusion Criteria:
- Patient has previously received chemotherapy
- Patient has received or will receive radiation therapy to the abdomen or pelvis in
the week prior to treatment
- Nausea or vomiting in the 24 hour period prior to commencing chemotherapy
- Use of antiemetics within 24 hours of the study period
- Patient has an active infection (e.g. pneumonia) or any uncontrolled disease (e.g.
diabetes, gastrointestinal obstruction), which in the opinion of the investigator
might confound the results of the study or pose unwarranted risk. Patients with
controlled diabetes are eligible.
- Patient currently uses any illicit drugs, including marijuana, or has current
evidence of alcohol abuse as determined by the investigator.
- Patient is mentally incapacitated or has a significant emotional or psychiatric
disorder that in the opinion of the investigator precludes study entry.
- Patient has a history of hypersensitivity or contraindication to granisetron or
dexamethasone.
- Patient is taking any systemic corticosteroid therapy at any dose. Topical or
inhaled steroids are permitted.
- Use of benzodiazepines in the 48 hours prior to the study period with the exception
of a single dose if used for sleeping.
- Abnormal laboratory values:
- Absolute neutrophil count < 1.5 X 10^9/L
- Platelet count < 100 X 10^9/L
- Liver transaminases > 2.5 X upper limit of normal
- Bilirubin > 1.5 X upper limit of normal
- Creatinine > 1.5 X upper limit of normal
- Patients who will receive a different chemotherapy regimen in Cycle 2 than in Cycle
1. Changes in the dose of the same chemotherapy agents are permitted if required for
toxicity.
- Refusal to give informed consent.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Outcome Measure:
Patient preference for the dexamethasone or the placebo arm as assessed by asking the patient whether they preferred treatment period 1 or treatment period 2
Outcome Time Frame:
dexamethasone for one cycle of chemotherapy and placebo for one cycle
Safety Issue:
No
Principal Investigator
Ian Tannock, MD PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University Health Network University of Toronto
Authority:
Canada: Health Canada
Study ID:
MDJV2
NCT ID:
NCT00152867
Start Date:
January 2005
Completion Date:
September 2010
Related Keywords:
- Cancer
- Emesis
- Nausea
- quality of life
- dexamethasone
- emesis
- Nausea
- Vomiting
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