MEGESTROL-ACETATE AND AMINOGLUTETHIMIDE HYDROCORTISONE IN SEQUENCE ORIN COMBINATION AS 2ND-LINE ENDOCRINE THERAPY OF ESTROGEN RECEPTOR-POSITIVE METASTATIC BREAST-CANCER - A SOUTHWEST-ONCOLOGY-GROUP PHASE-III TRIAL/

Purpose: A phase III randomized trial was performed to determine wheth er combination hormonal therapy with aminoglutethimide (AG) and hydroc ortisone (HC) plus megestrol acetate (MA) improved response rates, res ponse duration, or increased survival over the sequential use of each hormone in women with estrogen receptor-positive metastatic breast can cer (MBC) who had maintained stable disease for at least 6 months or r esponded to tamoxifen. Patients and Methods: Two hundred eighty-eight postmenopausal women with progressive estrogen receptor-positive MBC w ere randomly selected to receive MA 40 mg four times daily (arm I), AG 250 mg four times daily with HC 40 mg daily in divided doses (arm II) , versus the combination of MA plus AG given at the same dosages (arm III). Patients on arms I and II who progressed after an adequate trial were crossed over to the other treatment arm. Results: Two hundred th irty-five eligible patients were evaluated for response, time to treat ment failure, and survival. Response was only reported for patients wi th measurable disease and was not statistically different among the th ree arms, There were two partial responses (PRs) on MA (6%), four comp lete responses (CRs) and six PRs on AG (24%), and eight PRs and three CRs on MA plus AG (23%) in 32, 42, and 48 measurable patients, respect ively. Median times to treatment failure were also similar at 5, 4, an d 7 months. Survival was also not statistically different among the th ree arms at 26, 27, and 26 months for arms I, II, and III, respectivel y, Toxicity was greater in the two AG arms with respect to fatigue, na usea and vomiting, and rash. Conclusion: With the exception of toxicit y, there is no response, time to treatment failure, or survival benefi t for any one group when comparing MA, AG, or the combination at their stated doses in women with estrogen receptor-positive MBC who had pre viously responded to or stabilized with tamoxifen. (C) 1997 by America n Society of Clinical Oncology.