Trial Information

Comparison of Hypnotherapy Versus Gabapentin in the Treatment of Hot Flashes in Breast Cancer Survivors or Women at Risk of Developing Breast Cancer.

Roughly half of women diagnosed with pre-menopausal breast cancer will have hormone
receptor-positive tumors, which will make them candidates for anti-estrogen therapies. Both
endocrine therapy and ovarian ablation have also been shown to improve outcomes in this
population.

Hot flashes are a frequent side effect in women receiving anti-estrogen therapy for breast
cancer, and have been shown to have a significant impact on patients' quality of life. For
example, it has been reported that hot flashes in breast cancer survivors are more severe
and result in a more significant impact on quality of life measures when compared with
healthy women.

Hormone replacement, the gold standard for the treatment of hot flashes in postmenopausal
women, is contraindicated in this population. Non-hormonal drug therapies have been explored
for the treatment of hot flashes in this population of women with moderate results. In
randomized controlled trials, venlafaxine has been shown to reduce self-reported hot flashes
in patients with breast cancer by 25-61%. However, selective serotonin re-uptake inhibitors
(SSRIs) and selective norepinephrine re-uptake inhibitors (SNRIs) may interfere with the
metabolism of tamoxifen, a common treatment for estrogen-receptor positive breast cancers,
by inhibiting the cytochrome P450 2D6 (CYP2D6) enzyme. Gabapentin is a gamma-aminobutyric
acid (GABA) analogue commonly used for the treatment of seizure disorders and neuropathic
pain. There is some evidence to demonstrate its efficacy in hot flashes to be equivalent to
estrogen and superior to antidepressants in postmenopausal women.

In a pilot study of 22 women with breast cancer on tamoxifen, the use of gabapentin for four
weeks reduced the frequency of hot flashes by 44.2%, and decreased the hot flash severity
scores by 52.6%. These results were confirmed in a larger study of 420 breast cancer
survivors who were randomized to receive gabapentin 300mg/d, gabapentin 900mg/d, or placebo.
The 900mg/d dose of gabapentin was the most effective; decreasing the frequency of hot
flashes by 49% at four weeks. In the group receiving 900mg of gabapentin daily, there was a
12% withdrawal rate at 4 weeks, and 17% at 8 weeks, owing to side effects and subjective
inefficacy.

Hypnosis or hypnotherapy, defined as the induction of a deeply relaxed condition that allows
the patient to suspend critical faculties and allow suggestibility, has been shown to be
effective in not only reducing the daily frequency of hot flashes (by 59%), but also in
improving quality of life variables such as insomnia in patients with breast cancer.
However, this therapy has never been compared directly to pharmacotherapy in the treatment
of therapy-induced hot flashes in patients with breast cancer.

In response to the NCI's 2006 initiatives to expand the goals of clinical trials and include
symptom management studies, we are interested in evaluating the role of complementary and
alternative therapies for improvement of symptoms in women with breast cancer. This trial is
to determine whether hypnotherapy, administered in a standard way, can improve the frequency
of hot flashes and breast cancer specific quality of life in women diagnosed with
pre-menopausal breast cancer. We propose to evaluate this through a pilot feasibility study
which will randomize participants to an eight week course of gabapentin or hypnosis.