Journal of Clinical Oncology, Vol 15, 2494-2501, Copyright © 1997 by American Society of Clinical Oncology
Megestrol acetate and aminoglutethimide/hydrocortisone in sequence or in combination as second-line endocrine therapy of estrogen receptor- positive metastatic breast cancer: a Southwest Oncology Group phase III trial
CA Russell, SJ Green, J O'Sullivan, HE Hynes, GT Budd, JE Congdon, S Martino and CK Osborne
University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, USA.
PURPOSE: A phase III randomized trial was performed to determine whether
combination hormonal therapy with aminoglutethimide (AG) and hydrocortisone
(HC) plus megestrol acetate (MA) improved response rates, response
duration, or increased survival over the sequential use of each hormone in
women with estrogen receptor-positive metastatic breast cancer (MBC) who
had maintained stable disease for at least 6 months or responded to
tamoxifen. PATIENTS AND METHODS: Two hundred eighty-eight postmenopausal
women with progressive estrogen receptor- positive MBC were 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 thirty-five eligible patients were
evaluated for response, time to treatment failure, and survival. Response
was only reported for patients with measurable disease and was not
statistically different among the three arms. There were two partial
responses (PRs) on MA (6%), four complete 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, respectively. Median times to treatment failure were
also similar at 5, 4, and 7 months. Survival was also not statistically
different among the three arms at 26, 27, and 26 months for arms I, II, and
III, respectively. Toxicity was greater in the two AG arms with respect to
fatigue, nausea and vomiting, and rash. CONCLUSION: With the exception of
toxicity, there is no response, time to treatment failure, or survival
benefit for any one group when comparing MA, AG, or the combination at
their stated doses in women with estrogen receptor-positive MBC who had
previously responded to or stabilized with tamoxifen.
