Trial Information

Venlafaxine for Hot Flashes After Breast Cancer

Hot flashes are the most severe and fourth most prevalent menopausal symptom reported by
women with breast cancer. Hot flashes affect over 65% of this population, with 59% rating
the symptom as severe and 44% reporting they are extremely distressed by the symptom.
Despite the high prevalence, severity and distress associated with this symptom, the
scientific basis for managing hot flashes in women with breast cancer is limited. This
randomized, double-blind, placebo-controlled crossover trial examines the effectiveness and
toxicity of sustained release venlafaxine hydrochloride (37.5 mg po qd) on hot flashes in
women following treatment for breast cancer. Venlafaxine is a phenylethylamine derivative
that potently inhibits the reuptake of neuronal serotonin and norepinephrine and weakly
inhibits the reuptake of dopamine. A secondary aim of this project is to examine the impact
of hot flashes on psychological, behavioral, and physical outcomes. This study is based on
the Wickham Symptom Management Model which depicts interrelationships between symptoms,
symptom management strategies, and symptom management outcomes. Participants (n = 80) who
are at least one month post-completion of surgery, radiation, and/or chemotherapy and who
have been on tamoxifen (if prescribed) for at least six weeks will complete a two-week
baseline hot flash assessment and be randomized to one arm of the crossover trial. At the
end of the first six-week arm, participants will crossover to the opposite study arm for an
additional six weeks. Outcomes to be assessed include effectiveness of the intervention (hot
flash frequency, severity, distress and magnitude), toxicity of the intervention (subjective
preference, side effects), psychological outcomes (mood disturbance), behavioral outcomes
(quality of life, interference with daily activities) and physical outcomes (fatigue and
sleep disturbance). Hot flashes will be measured daily, using a subjective, prospective
diary methodology, and weekly, using objective state-of-the art 24-hour physiological
monitoring of sternal skin conductance. Other outcomes will be measured weekly. Compliance
with the intervention/placebo will be assessed weekly using medication blister pack cards.
Timing of outcome assessments is based on limitations of the physiological monitoring device
and expected timing of treatment effects. Summary statistics (i.e., mean, slope, maximum
response, range, proportion, achievable difference) will be used to effectively reduce the
design to a 2 X 2 crossover and data will be analyzed accordingly (i.e., t-tests, linear
regression, GEE, mixed model). Study findings will significantly contribute to the
scientific basis of hot flash management in women following treatment for breast cancer.