Future use of selective estrogen receptor modulators and aromatase inhibitors.

2.50
Hdl Handle:
http://hdl.handle.net/10541/83194
Title:
Future use of selective estrogen receptor modulators and aromatase inhibitors.
Authors:
Howell, Anthony ( 0000-0002-3879-5991 )
Abstract:
Selective estrogen receptor modulators (SERMs) may act as estrogens or antiestrogens depending on the cell and tissue targets. The triphenylethylene SERMs are represented by tamoxifen and toremifene and a new agent with a novel carboxylic acid side chain (GW5638). Because of isomerization in the triphenylethylene molecule, "fixed ring" SERMs were introduced. The major one in development is the benzothiophene arzoxiphene (LY353381), which is now in Phase III clinical trial versus tamoxifen. A fourth group of SERMs is based on the estrogen molecule and comprises the so-called "pure" antiestrogen ICI 182,780 (fulvestrant, Faslodex) and a new oral analogue just entering trials, SR16234. The steroidal aromatase inhibitors [AIs (40H androstenedione 'and exemestane)] inactivate aromatase, whereas the triazole AIs (anastrozole and letrozole) inhibit the enzyme via the heme prosthetic group. Thus, there are two groups of AIs that show relative non-cross-resistance in advanced breast cancer and four groups of SERMs that also show a high degree of non-cross-resistance. With six different treatments and six or more clinical situations (prevention, neoadjuvant, adjuvant, and first- and second-line treatments for advanced disease) in which they may be used, the possible combinations of treatment are enormous. At present, we have few clinical pointers to optimal sequence of treatments. Now that most of the appropriate comparative trials have been performed, it may be the time to initiate novel approaches. These include alternating and sequential treatments, preferably with treatments changed before overt progression occurs.
Affiliation:
CRC Department of Medical Oncology, University of Manchester, Christie Hospital, United Kingdom.
Citation:
Future use of selective estrogen receptor modulators and aromatase inhibitors. 2001, 7 (12 Suppl):4402s-4410s; discussion 4411s-4412s Clin. Cancer Res.
Journal:
Clinical Cancer Research
Issue Date:
Dec-2001
URI:
http://hdl.handle.net/10541/83194
PubMed ID:
11916232
Type:
Article
Language:
en
ISSN:
1078-0432
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorHowell, Anthony-
dc.date.accessioned2009-10-01T12:26:57Z-
dc.date.available2009-10-01T12:26:57Z-
dc.date.issued2001-12-
dc.identifier.citationFuture use of selective estrogen receptor modulators and aromatase inhibitors. 2001, 7 (12 Suppl):4402s-4410s; discussion 4411s-4412s Clin. Cancer Res.en
dc.identifier.issn1078-0432-
dc.identifier.pmid11916232-
dc.identifier.urihttp://hdl.handle.net/10541/83194-
dc.description.abstractSelective estrogen receptor modulators (SERMs) may act as estrogens or antiestrogens depending on the cell and tissue targets. The triphenylethylene SERMs are represented by tamoxifen and toremifene and a new agent with a novel carboxylic acid side chain (GW5638). Because of isomerization in the triphenylethylene molecule, "fixed ring" SERMs were introduced. The major one in development is the benzothiophene arzoxiphene (LY353381), which is now in Phase III clinical trial versus tamoxifen. A fourth group of SERMs is based on the estrogen molecule and comprises the so-called "pure" antiestrogen ICI 182,780 (fulvestrant, Faslodex) and a new oral analogue just entering trials, SR16234. The steroidal aromatase inhibitors [AIs (40H androstenedione 'and exemestane)] inactivate aromatase, whereas the triazole AIs (anastrozole and letrozole) inhibit the enzyme via the heme prosthetic group. Thus, there are two groups of AIs that show relative non-cross-resistance in advanced breast cancer and four groups of SERMs that also show a high degree of non-cross-resistance. With six different treatments and six or more clinical situations (prevention, neoadjuvant, adjuvant, and first- and second-line treatments for advanced disease) in which they may be used, the possible combinations of treatment are enormous. At present, we have few clinical pointers to optimal sequence of treatments. Now that most of the appropriate comparative trials have been performed, it may be the time to initiate novel approaches. These include alternating and sequential treatments, preferably with treatments changed before overt progression occurs.en
dc.language.isoenen
dc.subjectBreast Canceren
dc.subjectOestrogensen
dc.subjectCancer Recurrenceen
dc.subjectHormone-Dependent Canceren
dc.subjectOestrogen Receptorsen
dc.subject.meshAromatase Inhibitors-
dc.subject.meshBreast Neoplasms-
dc.subject.meshClinical Trials as Topic-
dc.subject.meshEnzyme Inhibitors-
dc.subject.meshEstrogens-
dc.subject.meshFemale-
dc.subject.meshForecasting-
dc.subject.meshHumans-
dc.subject.meshNeoplasm Recurrence, Local-
dc.subject.meshNeoplasms, Hormone-Dependent-
dc.subject.meshReceptors, Estrogen-
dc.subject.meshSelective Estrogen Receptor Modulators-
dc.titleFuture use of selective estrogen receptor modulators and aromatase inhibitors.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Medical Oncology, University of Manchester, Christie Hospital, United Kingdom.en
dc.identifier.journalClinical Cancer Researchen
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