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dc.contributor.authorHowell, Anthony
dc.contributor.authorDeFriend, D J
dc.contributor.authorRobertson, J F
dc.contributor.authorBlamey, R W
dc.contributor.authorAnderson, L
dc.contributor.authorAnderson, Elizabeth
dc.contributor.authorSutcliffe, F A
dc.contributor.authorWalton, P
dc.date.accessioned2010-04-06T10:13:11Z
dc.date.available2010-04-06T10:13:11Z
dc.date.issued1996-07
dc.identifier.citationPharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer. 1996, 74 (2):300-8 Br. J. Canceren
dc.identifier.issn0007-0920
dc.identifier.pmid8688341
dc.identifier.urihttp://hdl.handle.net/10541/95635
dc.description.abstractWe have assessed the pharmacokinetics, pharmacological and anti-tumour effects of the specific steroidal anti-oestrogen ICI 182780 in 19 patients with advanced breast cancer resistant to tamoxifen. The agent was administered as a monthly depot intramuscular injection. Peak levels of ICI 182780 occurred a median of 8-9 days after dosing and then declined but were above the projected therapeutic threshold at day 28. Cmax during the first month was 10.5 ng/ml-1 and during the sixth month was 12.6 ng ml-1. The AUCs were 140.5 and 206.8 ng day ml-1 on the first and sixth month of dosing respectively, suggesting some drug accumulation. Luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels rose after withdrawal of tamoxifen and then plateaued, suggesting no effect of ICI 182780 on the pituitary-hypothalamic axis. There were no significant changes in serum levels of prolactin, sex hormone-binding globulin (SHBG) or lipids. Side-effects were infrequent. Hot-flushes and sweats were not induced and there was no apparent effect of treatment upon the endometrium or vagina. Thirteen (69%) patients responded (seven had partial responses and six showed "no change' responses) to ICI 182780, after progression on tamoxifen, for a median duration of 25 months. Thus ICI 182780, given by monthly depot injection, and at the drug levels described, is an active second-line anti-oestrogen without apparent negative effects on the liver, brain or genital tract and warrants further evaluation in patients with advanced breast cancer.
dc.language.isoenen
dc.subjectBreast Canceren
dc.subjectCancer Drug Resistanceen
dc.subjectOestrogen Antagonistsen
dc.subject.meshAged
dc.subject.meshAntineoplastic Agents
dc.subject.meshBreast Neoplasms
dc.subject.meshDrug Resistance, Neoplasm
dc.subject.meshEstradiol
dc.subject.meshEstrogen Antagonists
dc.subject.meshFemale
dc.subject.meshFollicle Stimulating Hormone
dc.subject.meshHumans
dc.subject.meshLuteinizing Hormone
dc.subject.meshMiddle Aged
dc.subject.meshSex Hormone-Binding Globulin
dc.titlePharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Medical Oncology, University of Manchester, Christie Hospital, UK.en
dc.identifier.journalBritish Journal of Canceren
html.description.abstractWe have assessed the pharmacokinetics, pharmacological and anti-tumour effects of the specific steroidal anti-oestrogen ICI 182780 in 19 patients with advanced breast cancer resistant to tamoxifen. The agent was administered as a monthly depot intramuscular injection. Peak levels of ICI 182780 occurred a median of 8-9 days after dosing and then declined but were above the projected therapeutic threshold at day 28. Cmax during the first month was 10.5 ng/ml-1 and during the sixth month was 12.6 ng ml-1. The AUCs were 140.5 and 206.8 ng day ml-1 on the first and sixth month of dosing respectively, suggesting some drug accumulation. Luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels rose after withdrawal of tamoxifen and then plateaued, suggesting no effect of ICI 182780 on the pituitary-hypothalamic axis. There were no significant changes in serum levels of prolactin, sex hormone-binding globulin (SHBG) or lipids. Side-effects were infrequent. Hot-flushes and sweats were not induced and there was no apparent effect of treatment upon the endometrium or vagina. Thirteen (69%) patients responded (seven had partial responses and six showed "no change' responses) to ICI 182780, after progression on tamoxifen, for a median duration of 25 months. Thus ICI 182780, given by monthly depot injection, and at the drug levels described, is an active second-line anti-oestrogen without apparent negative effects on the liver, brain or genital tract and warrants further evaluation in patients with advanced breast cancer.


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