title: A cancer research (UK) randomized phase II study of idoxifene in patients with locally advanced/metastatic breast cancer resistant to tamoxifen.
abstract: Idoxifene is a novel selective oestrogen receptor modulator (SERM) which had greater binding affinity for the oestrogen receptor (ER) and reduced agonist activity compared with tamoxifen in preclinical studies. In a randomized phase II trial in 56 postmenopausal patients with progressive locally advanced/metastatic breast cancer we assessed whether idoxifene showed evidence of activity compared with an increased 40 mg/day dose of tamoxifen in patients who had previously demonstrated resistance to the standard 20 mg/day dose of tamoxifen. Of 47 patients eligible for response (25 idoxifene, 22 tamoxifen), two partial responses and two disease stabilizations (SD) for >6 months were seen with idoxifene (overall clinical benefit rate 16%, 95% CI 4.5-36.1%). The median duration of clinical benefit was 9.8 months. In contrast, no objective responses were seen with the increased 40 mg/day dose of tamoxifen, although two patients had SD for 7 and 14 months (clinical benefit rate 9%, 95% CI 1.1-29.2%). Idoxifene was well tolerated and the reported possible drug-related toxicities were similar in frequency to those with tamoxifen (hot flushes 13% vs 15%, mild nausea 20% vs 15%). Endocrine and lipid analysis in both groups showed a similar significant fall in serum follicle-stimulating hormone and luteinizing hormone after 4 weeks, together with a significant rise in sex hormone binding globulin levels and 11% reduction in serum cholesterol levels. In conclusion, while idoxifene was associated with only modest evidence of clinical activity in patients with tamoxifen-resistant breast cancer, its toxicity profile and effects on endocrine/lipid parameters were similar to those of tamoxifen.
authors.affiliation: Cancer Research UK, Lincoln's Inn Fields, London, WC2A 3PX, UK.
authors.forename: S R D
authors.initials: SR
authors.lastname: Johnston
authors.forename: L A
authors.initials: LA
authors.lastname: Gumbrell
authors.forename: T R J
authors.initials: TR
authors.lastname: Evans
authors.forename: R E
authors.initials: RE
authors.lastname: Coleman
authors.forename: I E
authors.initials: IE
authors.lastname: Smith
authors.forename: C J
authors.initials: CJ
authors.lastname: Twelves
authors.forename: M
authors.initials: M
authors.lastname: Soukop
authors.forename: D W
authors.initials: DW
authors.lastname: Rea
authors.forename: H M
authors.initials: HM
authors.lastname: Earl
authors.forename: A
authors.initials: A
authors.lastname: Howell
authors.forename: A
authors.initials: A
authors.lastname: Jones
authors.forename: P
authors.initials: P
authors.lastname: Canney
authors.forename: T J
authors.initials: TJ
authors.lastname: Powles
authors.forename: B P
authors.initials: BP
authors.lastname: Haynes
authors.forename: B
authors.initials: B
authors.lastname: Nutley
authors.forename: R
authors.initials: R
authors.lastname: Grimshaw
authors.forename: M
authors.initials: M
authors.lastname: Jarman
authors.forename: G W
authors.initials: GW
authors.lastname: Halbert
authors.forename: M
authors.initials: M
authors.lastname: Brampton
authors.forename: J
authors.initials: J
authors.lastname: Haviland
authors.forename: M
authors.initials: M
authors.lastname: Dowsett
authors.forename: R C
authors.initials: RC
authors.lastname: Coombes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001682:Biological Availability; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004311:Double-Blind Method; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011956:Receptors, Cell Surface / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; C063572:sex hormone-binding globulin receptor; D013629:Tamoxifen; C071362:idoxifene