Pharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer.

2.50
Hdl Handle:
http://hdl.handle.net/10541/95635
Title:
Pharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer.
Authors:
Howell, Anthony ( 0000-0002-3879-5991 ) ; DeFriend, D J; Robertson, J F; Blamey, R W; Anderson, L; Anderson, Elizabeth; Sutcliffe, F A; Walton, P
Abstract:
We 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.
Affiliation:
CRC Department of Medical Oncology, University of Manchester, Christie Hospital, UK.
Citation:
Pharmacokinetics, 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. Cancer
Journal:
British Journal of Cancer
Issue Date:
Jul-1996
URI:
http://hdl.handle.net/10541/95635
PubMed ID:
8688341
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorHowell, Anthonyen
dc.contributor.authorDeFriend, D Jen
dc.contributor.authorRobertson, J Fen
dc.contributor.authorBlamey, R Wen
dc.contributor.authorAnderson, Len
dc.contributor.authorAnderson, Elizabethen
dc.contributor.authorSutcliffe, F Aen
dc.contributor.authorWalton, Pen
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.en
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

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