Quality of life of patients undergoing androgen deprivation is an issue that has received limited attention in the past but is currently being actively evaluated in clinical trials. This issue becomes more important as patients with longer life expectancy and no metastatic disease are treated for longer durations.
The type and extent of potential long-term androgen deprivation-related side effects, such as osteoporosis and effects on muscle mass, heart, and lipids, are not clear. However, the association of impotence and hot flashes with the two leading modalities of androgen deprivation--bilateral orchiectomy and luteinizing hormone-re- leasing hormone (LHRH) agonists--is better documented. These side effects seem to be the most bothersome from the patient's perspective. While not a serious adverse effect, hot flashes, when severe, are annoying and interfere with quality of life, although they rarely warrant discontinuation of therapy.
Dr. Smith provides a fair assessment of hot flashes and their management in patients undergoing androgen deprivation. The cause of vasomotor hot flashes is not entirely clear, but Dr. Smith discusses potential physiologic mechanisms.
Therapy of hot flashes is not always necessary and is dictated by the severity of symptoms. As outlined in the article, various therapeutic interventions, both hormonal and nonhormonal, are available. However, therapy must be individualized, weighing the risks vs benefits of such treatment.
Of the available remedies, hormonal agents, such as estrogens(Drug information on estrogens), lowdose megestrol acetate, and cyproterone(Drug information on cyproterone) acetate, are reported to be the most effective. Estrogens are associated with cardiovascular adverse effects, gynecomastia, and breast tenderness, however, and cyproterone acetate is not commercially available in this country. Low-dose megestrol(Drug information on megestrol) acetate could be offered as an effective treatment of hot flashes, although the possible effects of long-term, low-dose therapy with this agent on the course of prostate cancer and other biologic systems are unknown.
In general, nonhormonal agents are not very effective. In hormonally treated breast cancer patients, the palliation of hot flashes has not been limited to prescribed medications but also includes agents that might be viewed as "natural" remedies, such as vitamin E(Drug information on vitamin e), ginseng, and garlic tablets. Anecdotally, these substances seem to afford some symptomatic relief in certain hormonally treated prostate cancer patients.
Intermittent Androgen Deprivation?
Recent interest in improving the efficacy of hormone therapy while enhancing quality of life has led to the clinical investigation of intermittent androgen deprivation. This involves, on average, 8 to 10 months of treatment with an LHRH agonist plus an antiandrogen to ensure a sustained suppression of prostate-specific antigen (PSA) to a nadir below the normal range, followed by an off-therapy period. The off-therapy period will last as long as the PSA does not rise above an arbitrarily determined level of 10 to 20 ng/mL. The cycle is then repeated.
Preclinical data suggest a therapeutic advantage of intermittent androgen deprivation over continuous therapy. The potential for full recovery from medical castration makes this approach feasible, as is suggested by the preliminary clinical data. Serum testosterone returns to the normal range within 8 weeks on average. This generally results in an improvement in patients' sense of well-being in addition to a marked reduction in or elimination of hot flashes.
The efficacy of intermittent androgen suppression relative to the continuous approach is currently being investigated in patients with newly diagnosed metastatic prostate cancer in a phase III randomized intergroup trial (INT-0162 ). The intermittent approach is a very promising alternative to continuous androgen deprivation, particularly when long-term therapy is entertained, as it appears to minimize such side effects as hot flashes. However, patients must be counseled about its investigational nature.