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Cancer Research UK Phase I/II Committee. A Cancer Research (UK) randomised phase II study of idoxifene in patients with locally advanced / metastatic breast cancer resistant to tamoxifen

Cancer Research UK Phase I/II Committee. A Cancer Research (UK) randomised phase II study of idoxifene in patients with locally advanced / metastatic breast cancer resistant to tamoxifen
Cancer Research UK Phase I/II Committee. A Cancer Research (UK) randomised phase II study of idoxifene in patients with locally advanced / metastatic breast cancer resistant to tamoxifen
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
0344-5704
341-348
Johnston, S.R.
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Gumbrell, L.A.
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Evans, T.R.
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Coleman, R.E.
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Smith, I.E.
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Twelves, C.J.
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Soukop, M.
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Rea, D.W.
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Earl, H.M.
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Howell, A.
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Jones, A.
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Canney, P.
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Powels, T.J.
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Haynes, B.P.
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Nutley, B.
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Grimshaw, R.
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Jarman, Megan
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Halbert, G.W.
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Brampton, M.
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Haviland, J.S.
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Dowsett, M.
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Coombes, R.C.
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Johnston, S.R.
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Gumbrell, L.A.
c053e86a-26bc-4cfb-9b5f-bd29c30413a6
Evans, T.R.
b5ccb539-723c-4d3e-906d-0d36769685f3
Coleman, R.E.
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Smith, I.E.
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Twelves, C.J.
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Soukop, M.
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Rea, D.W.
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Earl, H.M.
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Howell, A.
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Jones, A.
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Canney, P.
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Powels, T.J.
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Haynes, B.P.
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Nutley, B.
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Grimshaw, R.
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Jarman, Megan
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Halbert, G.W.
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Brampton, M.
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Haviland, J.S.
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Dowsett, M.
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Coombes, R.C.
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Johnston, S.R., Gumbrell, L.A., Evans, T.R., Coleman, R.E., Smith, I.E., Twelves, C.J., Soukop, M., Rea, D.W., Earl, H.M., Howell, A., Jones, A., Canney, P., Powels, T.J., Haynes, B.P., Nutley, B., Grimshaw, R., Jarman, Megan, Halbert, G.W., Brampton, M., Haviland, J.S., Dowsett, M. and Coombes, R.C. (2004) Cancer Research UK Phase I/II Committee. A Cancer Research (UK) randomised phase II study of idoxifene in patients with locally advanced / metastatic breast cancer resistant to tamoxifen. Cancer Chemotherapy and Pharmacology, 53 (4), 341-348. (doi:10.1007/s00280-003-0733-6).

Record type: Article

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

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Published date: 2004
Organisations: Faculty of Health Sciences

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Local EPrints ID: 365430
URI: http://eprints.soton.ac.uk/id/eprint/365430
ISSN: 0344-5704
PURE UUID: ed701c50-d981-4c89-bd24-d5dd69ae1cfc

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Date deposited: 05 Jun 2014 10:41
Last modified: 16 Jul 2019 21:04

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Contributors

Author: S.R. Johnston
Author: L.A. Gumbrell
Author: T.R. Evans
Author: R.E. Coleman
Author: I.E. Smith
Author: C.J. Twelves
Author: M. Soukop
Author: D.W. Rea
Author: H.M. Earl
Author: A. Howell
Author: A. Jones
Author: P. Canney
Author: T.J. Powels
Author: B.P. Haynes
Author: B. Nutley
Author: R. Grimshaw
Author: Megan Jarman
Author: G.W. Halbert
Author: M. Brampton
Author: J.S. Haviland
Author: M. Dowsett
Author: R.C. Coombes

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