title: High dose toremifene for estrogen and progesterone receptor negative metastatic breast cancer: a phase II trial of the Cancer and Leukemia Group B (CALGB).
abstract: In pre-clinical and limited clinical studies, high doses ( > or = 200 mg/day) of the triphenylethylene derivative toremifene showed activity in estrogen receptor (ER) negative and ER-unknown metastatic breast cancer after progression on tamoxifen, and a mechanism of action independent of hormone receptor binding was speculated. The CALGB conducted a Phase II trial (CALGB 8945) to test the efficacy of high dose toremifene in a population of patients who had hormone receptor-negative, metastatic breast cancer with limited prior chemotherapy exposure, good performance status, and measurable disease. Twenty eligible patients received toremifene at a dose of 400 mg/day orally for 8 weeks. Toxicity was minimal. Nausea was reported by 20% of the patients, lightheadedness by 20%, weight loss by 20%, and hot flashes by 15%. There was no grade 3-4 toxicity. No objective responses were observed, and 5 of 6 patients with stable disease at 8 weeks developed progressive disease at 11 to 33 weeks. High dose toremifene (400 mg/day) is well-tolerated but imparts no detectable activity in hormone receptor-negative, metastatic breast cancer.
authors.affiliation: Section of Hematology-Oncology, Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC 27157-1082, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Perry
authors.forename: D A
authors.initials: DA
authors.lastname: Berry
authors.forename: R B
authors.initials: RB
authors.lastname: Weiss
authors.forename: D M
authors.initials: DM
authors.lastname: Hayes
authors.forename: D B
authors.initials: DB
authors.lastname: Duggan
authors.forename: I C
authors.initials: IC
authors.lastname: Henderson
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D017312:Toremifene / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D017312:Toremifene