title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Russell
authors.forename: S J
authors.initials: SJ
authors.lastname: Green
authors.forename: J
authors.initials: J
authors.lastname: O'Sullivan
authors.forename: H E
authors.initials: HE
authors.lastname: Hynes
authors.forename: G T
authors.initials: GT
authors.lastname: Budd
authors.forename: J E
authors.initials: JE
authors.lastname: Congdon
authors.forename: S
authors.initials: S
authors.lastname: Martino
authors.forename: C K
authors.initials: CK
authors.lastname: Osborne
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000616:Aminoglutethimide / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D008535:Megestrol / Q000008:administration & dosage; D008875:Middle Aged; D011960:Receptors, Estrogen; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D000616:Aminoglutethimide; D008535:Megestrol; D006854:Hydrocortisone