Goodwin, J.W., Green, S.J., Moinpour, C.M., Bearden, J.D., III, Giguere, J.K., Jiang, C.S., … Albain, K.S. (2008). Phase III randomized placebo-controlled trial of two doses of megestrol acetate as treatment for menopausal symptoms in women with breast cancer: southwest oncology group study 9626. Journal of Clinical Oncology, 26, 1650–1656.

Southwest Oncology Group Study 9626 evaluated  megestrol for management of menopausal symptoms in women with breast cancer. It compared two doses of megestrol acetate  versus placebo over six months. Participants were randomized to placebo, megestrol 20 mg, or megestrol 40 mg daily for three months. If success was achieved, treatment continued for three additional months. If not, the patient was unblinded and given megestrol 20 mg daily.

Participants: 288 patients with T 1-3, N0-1 breast cancer following surgery, chemotherapy, and at least four months of tamoxifen, if prescribed, were enrolled. 225 completed the trial.

This was a phase III, randomized, placebo-controlled, double-blind trial.

At the initial evaluation, patients completed a seven-day patient daily log of hot flashes with re-evaluation at three and six months. The primary endpoint was differences in the probability of hot flash reduction in three comparison groups.  Instruments included:

• The patient report of menopausal symptoms
• The symptom log
• National Cancer Institute Common Toxicity Criteria, version 2.
• Performance status assessed using ECOG scale

At three months, improvement was 14% with placebo, 65% withmegestrol acetate 20 mg, and 48% with megestrol acetate 40 mg. Both doses were superior to placebo (p < .0001). Duration of effectiveness continued at six months. Megestrol 40 mg was not superior to megestrol 20 mg.

The recommended daily dose is 20 mg.

The study was not designed to evaluate long-term toxicities or relapse of symptoms with long-term use. Concern remains regarding the use of progestins in women with a history of breast cancer.