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Optimal management of breast cancer in the elderly patient: current perspectives

Identifieur interne : 001011 ( Pmc/Checkpoint ); précédent : 001010; suivant : 001012

Optimal management of breast cancer in the elderly patient: current perspectives

Auteurs : Olivia Le Saux [France] ; Bertrand Ripamonti [France] ; Amandine Bruyas [France] ; Olivier Bonin [France] ; Gilles Freyer [France] ; Marc Bonnefoy [France] ; Claire Falandry [France]

Source :

RBID : PMC:4293298

Abstract

Breast cancer (BC) is the most common female malignancy in the world and almost one third of cases occur after 70 years of age. Optimal management of BC in the elderly is a real challenge and requires a multidisciplinary approach, mainly because the elderly population is heterogeneous. In this review, we describe the various possibilities of treatment for localized or metastatic BC in an aging population. We provide an overview of the comprehensive geriatric assessment, surgery, radiotherapy, and adjuvant therapy for early localized BC and of chemotherapy and targeted therapies for metastatic BC. Finally, we attempt to put into perspective the necessary balance between the expected benefits and risks, especially in the adjuvant setting.


Url:
DOI: 10.2147/CIA.S50670
PubMed: 25609933
PubMed Central: 4293298


Affiliations:


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PMC:4293298

Le document en format XML

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</TEI>
<pmc article-type="review-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Clin Interv Aging</journal-id>
<journal-id journal-id-type="iso-abbrev">Clin Interv Aging</journal-id>
<journal-id journal-id-type="publisher-id">Clinical Interventions in Aging</journal-id>
<journal-title-group>
<journal-title>Clinical Interventions in Aging</journal-title>
</journal-title-group>
<issn pub-type="ppub">1176-9092</issn>
<issn pub-type="epub">1178-1998</issn>
<publisher>
<publisher-name>Dove Medical Press</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">25609933</article-id>
<article-id pub-id-type="pmc">4293298</article-id>
<article-id pub-id-type="doi">10.2147/CIA.S50670</article-id>
<article-id pub-id-type="publisher-id">cia-10-157</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Review</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Optimal management of breast cancer in the elderly patient: current perspectives</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Le Saux</surname>
<given-names>Olivia</given-names>
</name>
<xref ref-type="aff" rid="af1-cia-10-157">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ripamonti</surname>
<given-names>Bertrand</given-names>
</name>
<xref ref-type="aff" rid="af2-cia-10-157">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bruyas</surname>
<given-names>Amandine</given-names>
</name>
<xref ref-type="aff" rid="af3-cia-10-157">3</xref>
<xref ref-type="aff" rid="af4-cia-10-157">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bonin</surname>
<given-names>Olivier</given-names>
</name>
<xref ref-type="aff" rid="af4-cia-10-157">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Freyer</surname>
<given-names>Gilles</given-names>
</name>
<xref ref-type="aff" rid="af1-cia-10-157">1</xref>
<xref ref-type="aff" rid="af4-cia-10-157">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bonnefoy</surname>
<given-names>Marc</given-names>
</name>
<xref ref-type="aff" rid="af4-cia-10-157">4</xref>
<xref ref-type="aff" rid="af5-cia-10-157">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Falandry</surname>
<given-names>Claire</given-names>
</name>
<xref ref-type="aff" rid="af4-cia-10-157">4</xref>
<xref ref-type="aff" rid="af5-cia-10-157">5</xref>
<xref ref-type="corresp" rid="c1-cia-10-157"></xref>
</contrib>
</contrib-group>
<aff id="af1-cia-10-157">
<label>1</label>
Medical Oncology Unit, Lyon Sud University Hospital, Hospices Civils de Lyon, Pierre-Bénite, France</aff>
<aff id="af2-cia-10-157">
<label>2</label>
Gynaecology-Obstetrics Department, University Hospital, Saint-Etienne, France</aff>
<aff id="af3-cia-10-157">
<label>3</label>
Croix Rousse University Hospital, Hospices Civils de Lyon, Pierre-Bénite, France</aff>
<aff id="af4-cia-10-157">
<label>4</label>
Lyon University, Lyon, France</aff>
<aff id="af5-cia-10-157">
<label>5</label>
Geriatric Unit, Lyon Sud University Hospital, Hospices Civils de Lyon, Pierre-Bénite, France</aff>
<author-notes>
<corresp id="c1-cia-10-157">Correspondence: Claire Falandry, Geriatrics unit, Centre Hospitalier Lyon Sud, 69495 Pierre-Benite cedex, France, Tel +33 4 78 86 15 80, Fax +33 4 78 86 57 27, Email
<email>claire.falandry@chu-lyon.fr</email>
</corresp>
</author-notes>
<pub-date pub-type="collection">
<year>2015</year>
</pub-date>
<pub-date pub-type="epub">
<day>06</day>
<month>1</month>
<year>2015</year>
</pub-date>
<volume>10</volume>
<fpage>157</fpage>
<lpage>174</lpage>
<permissions>
<copyright-statement>© 2015 Le Saux et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License</copyright-statement>
<copyright-year>2015</copyright-year>
<license>
<license-p>The full terms of the License are available at
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</ext-link>
. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.</license-p>
</license>
</permissions>
<abstract>
<p>Breast cancer (BC) is the most common female malignancy in the world and almost one third of cases occur after 70 years of age. Optimal management of BC in the elderly is a real challenge and requires a multidisciplinary approach, mainly because the elderly population is heterogeneous. In this review, we describe the various possibilities of treatment for localized or metastatic BC in an aging population. We provide an overview of the comprehensive geriatric assessment, surgery, radiotherapy, and adjuvant therapy for early localized BC and of chemotherapy and targeted therapies for metastatic BC. Finally, we attempt to put into perspective the necessary balance between the expected benefits and risks, especially in the adjuvant setting.</p>
</abstract>
<kwd-group>
<title>Keywords</title>
<kwd>elderly</kwd>
<kwd>breast cancer</kwd>
<kwd>geriatric assessment</kwd>
<kwd>surgery</kwd>
<kwd>chemotherapy</kwd>
<kwd>radiotherapy</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group>
<table-wrap id="t1-cia-10-157" position="float">
<label>Table 1</label>
<caption>
<p>Neoadjuvant hormone therapy</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th valign="top" align="left" rowspan="1" colspan="1">Hormone therapy</th>
<th valign="top" align="left" rowspan="1" colspan="1">Reference</th>
<th valign="top" align="left" rowspan="1" colspan="1">Age, median and range (years)</th>
<th valign="top" align="left" rowspan="1" colspan="1">Study design and population</th>
<th valign="top" align="left" rowspan="1" colspan="1">Efficacy</th>
<th valign="top" align="left" rowspan="1" colspan="1">Toxicity</th>
</tr>
</thead>
<tbody>
<tr>
<td rowspan="2" valign="top" align="left" colspan="1">Exemestane 25 mg orally once daily for 4 months</td>
<td valign="top" align="left" rowspan="1" colspan="1">Mlineritsch et al
<xref rid="b198-cia-10-157" ref-type="bibr">198</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">71 (54–92)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Multicenter, Phase II, 80 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">ORR 34%
<break></break>
BCS 76%</td>
<td valign="top" align="left" rowspan="1" colspan="1">Grade 3 hot flushes 3.8%
<break></break>
Grade 2 bone pain 5%</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Tubiana-Hulin et al
<xref rid="b199-cia-10-157" ref-type="bibr">199</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">67.6 (52.1–92.2)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Multicenter, Phase II, 45 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">ORR (clinical) 73.3%
<break></break>
ORR (ultrasonographic) 45.2%
<break></break>
BCS 57.1%</td>
<td valign="top" align="left" rowspan="1" colspan="1">Grade 1–2 toxicity 69.6%</td>
</tr>
<tr>
<td rowspan="2" valign="top" align="left" colspan="1">Anastrozole (1 mg once daily for 3 months) versus tamoxifen</td>
<td valign="top" align="left" rowspan="1" colspan="1">Cataliotti et al
<xref rid="b200-cia-10-157" ref-type="bibr">200</xref>
PROACT trial</td>
<td valign="top" align="left" rowspan="1" colspan="1">67.3 (48.7–91.5)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Randomized, double-blind, multicenter, Phase III, 451 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">ORR 39.5% (ultrasound measurements) and 50% (caliper measurements) BCS 43%</td>
<td valign="top" align="left" rowspan="1" colspan="1">Nausea 20.6%
<break></break>
Hot flushes 8.3%</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Smith et al
<xref rid="b201-cia-10-157" ref-type="bibr">201</xref>
IMPACT trial</td>
<td valign="top" align="left" rowspan="1" colspan="1">73.2 (51.8–90.2)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Randomized, double-blind, multicenter, Phase III, 330 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">Clinical ORR 37%
<break></break>
Ultrasound ORR 24%
<break></break>
BCS 44%</td>
<td valign="top" align="left" rowspan="1" colspan="1">Hot flushes 18%</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Letrozole (2 mg once daily for 4 months) versus tamoxifen</td>
<td valign="top" align="left" rowspan="1" colspan="1">Eiermann et al
<xref rid="b202-cia-10-157" ref-type="bibr">202</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">68</td>
<td valign="top" align="left" rowspan="1" colspan="1">Multinational, randomized, double-blind, Phase IIb–III, 324 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">Clinical ORR 55%
<break></break>
Ultrasound response 35%
<break></break>
BCS 45%</td>
<td valign="top" align="left" rowspan="1" colspan="1">Hot flushes 20%</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="tfn1-cia-10-157">
<p>
<bold>Note:</bold>
Grading based upon NCI-CTC (National Cancer Institute Common Toxicity Criteria).</p>
</fn>
<fn id="tfn2-cia-10-157">
<p>
<bold>Abbreviations:</bold>
ORR, objective response rate; BCS, breast-conserving surgery; PROACT, Pre-Operative “Arimidex” Compared to Tamoxifen trial; IMPACT, Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen trial.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="t2-cia-10-157" position="float">
<label>Table 2</label>
<caption>
<p>Monochemotherapy regimens</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th valign="top" align="left" rowspan="1" colspan="1">Chemotherapy regimens</th>
<th valign="top" align="left" rowspan="1" colspan="1">Dosage</th>
<th valign="top" align="left" rowspan="1" colspan="1">Reference</th>
<th valign="top" align="left" rowspan="1" colspan="1">Age, median and range (years)</th>
<th valign="top" align="left" rowspan="1" colspan="1">Study design and population</th>
<th valign="top" align="left" rowspan="1" colspan="1">Line</th>
<th valign="top" align="left" rowspan="1" colspan="1">Efficacy</th>
<th valign="top" align="left" rowspan="1" colspan="1">Toxicity</th>
</tr>
</thead>
<tbody>
<tr>
<td rowspan="3" valign="top" align="left" colspan="1">Pegylated liposomal doxorubicin</td>
<td valign="top" align="left" rowspan="1" colspan="1">40 mg/m
<sup>2</sup>
every 28 days</td>
<td valign="top" align="left" rowspan="1" colspan="1">Falandry et al
<xref rid="b158-cia-10-157" ref-type="bibr">158</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">77 (71–89)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Multicenter, Phase II, 60 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First line</td>
<td valign="top" align="left" rowspan="1" colspan="1">ORR 20%
<break></break>
PFS 6.1 months
<break></break>
OS 15.7 months</td>
<td valign="top" align="left" rowspan="1" colspan="1">Febrile neutropenia 1.7%
<break></break>
Congestive heart failure 3.4%</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">40 mg/m
<sup>2</sup>
every 28 days</td>
<td valign="top" align="left" rowspan="1" colspan="1">Green et al
<xref rid="b203-cia-10-157" ref-type="bibr">203</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">72.3 (65–81)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Multicenter, Phase IV, 25 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First line</td>
<td valign="top" align="left" rowspan="1" colspan="1">TTP 5.7 months
<break></break>
OS 20.6 months</td>
<td valign="top" align="left" rowspan="1" colspan="1">Cardiac events 12%</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">20 mg/m
<sup>2</sup>
every 2 weeks</td>
<td valign="top" align="left" rowspan="1" colspan="1">Basso et al
<xref rid="b159-cia-10-157" ref-type="bibr">159</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">78 (70–93)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Multicenter, Phase II, 32 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First line (78.1%)</td>
<td valign="top" align="left" rowspan="1" colspan="1">ORR 33.3%
<break></break>
TTP 10.3 months</td>
<td valign="top" align="left" rowspan="1" colspan="1">No cardiac event 9.4% treatment interruption for toxicity</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Oral Idarubicin</td>
<td valign="top" align="left" rowspan="1" colspan="1">5 mg/day for 21 consecutive days, every 4 weeks</td>
<td valign="top" align="left" rowspan="1" colspan="1">Crivellari et al
<xref rid="b204-cia-10-157" ref-type="bibr">204</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">75 (65–81)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase II, 33 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First or second line</td>
<td valign="top" align="left" rowspan="1" colspan="1">PR 22%
<break></break>
SD 33%
<break></break>
TTP 3 months
<break></break>
OS 17 months</td>
<td valign="top" align="left" rowspan="1" colspan="1">Grade 4 neutropenia 6%
<break></break>
No cardiotoxicity reported
<break></break>
Two toxic deaths with 7.5 mg/day</td>
</tr>
<tr>
<td rowspan="2" valign="top" align="left" colspan="1">Capecitabine</td>
<td valign="top" align="left" rowspan="1" colspan="1">1,000 mg/m
<sup>2</sup>
twice daily</td>
<td valign="top" align="left" rowspan="1" colspan="1">Bajetta et al
<xref rid="b161-cia-10-157" ref-type="bibr">161</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">73 (65–89)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase II, 73 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First line (93%)</td>
<td valign="top" align="left" rowspan="1" colspan="1">ORR 34.9%
<break></break>
TTP 4 months</td>
<td valign="top" align="left" rowspan="1" colspan="1">2 toxic deaths with 1,250 mg/m
<sup>2</sup>
<break></break>
Low grade 3/4 AEs with 1,000 mg/m
<sup>2</sup>
</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">1,000 mg/m
<sup>2</sup>
twice daily for 14 days every 3 weeks</td>
<td valign="top" align="left" rowspan="1" colspan="1">De Sanctis et al
<xref rid="b162-cia-10-157" ref-type="bibr">162</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">76 (65–88)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase II, 75 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First line</td>
<td valign="top" align="left" rowspan="1" colspan="1">Disease control rate 81.3%</td>
<td valign="top" align="left" rowspan="1" colspan="1">Grade 3 events: diarrhea (12%), hand–foot syndrome (8%), mucositis (8%)</td>
</tr>
<tr>
<td rowspan="2" valign="top" align="left" colspan="1">Vinorelbine</td>
<td valign="top" align="left" rowspan="1" colspan="1">30 mg/m
<sup>2</sup>
/week for 13 weeks and then every 2 weeks</td>
<td valign="top" align="left" rowspan="1" colspan="1">Vogel et al
<xref rid="b205-cia-10-157" ref-type="bibr">205</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">72 (60–84)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Multicenter, Phase II, 56 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First line</td>
<td valign="top" align="left" rowspan="1" colspan="1">ORR 38%
<break></break>
TTP 6 months</td>
<td valign="top" align="left" rowspan="1" colspan="1">Febrile neutropenia 11%</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">70 mg/m
<sup>2</sup>
orally on days 1, 3, and 5, for 3 weeks every 4 weeks (maximum 12 cycles)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Addeo et al
<xref rid="b164-cia-10-157" ref-type="bibr">164</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">74 (70–84)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase II, 34 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First line</td>
<td valign="top" align="left" rowspan="1" colspan="1">ORR 38%
<break></break>
PFS 7.7 months
<break></break>
OS 15.9 months</td>
<td valign="top" align="left" rowspan="1" colspan="1">Febrile neutropenia 6%</td>
</tr>
<tr>
<td rowspan="2" valign="top" align="left" colspan="1">Paclitaxel</td>
<td valign="top" align="left" rowspan="1" colspan="1">80 mg/m
<sup>2</sup>
weekly for 3 weeks every 28 days</td>
<td valign="top" align="left" rowspan="1" colspan="1">Del Mastro et al
<xref rid="b165-cia-10-157" ref-type="bibr">165</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">74 (70–87)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase II, 46 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First line</td>
<td valign="top" align="left" rowspan="1" colspan="1">ORR 53.7%
<break></break>
PFS 9.7 months
<break></break>
OS 35.8 months</td>
<td valign="top" align="left" rowspan="1" colspan="1">Unacceptable toxicity: 15.2% (febrile neutropenia, severe allergic reaction, and cardiotoxicity)</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">80 mg/m
<sup>2</sup>
on days 1, 8, and 15 of a 28-day cycle (dose increase 90 mg/m
<sup>2</sup>
in absence of toxicity)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Ten Tije et al
<xref rid="b166-cia-10-157" ref-type="bibr">166</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">77 (71–84)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Multicenter, Phase II, 26 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First line</td>
<td valign="top" align="left" rowspan="1" colspan="1">ORR 38%
<break></break>
TTP 6.5 months</td>
<td valign="top" align="left" rowspan="1" colspan="1">Fatigue 67%
<break></break>
Neuropathy 39%</td>
</tr>
<tr>
<td rowspan="3" valign="top" align="left" colspan="1">Docetaxel</td>
<td valign="top" align="left" rowspan="1" colspan="1">36 mg/m
<sup>2</sup>
weekly for 6 consecutive weeks, followed by 2 weeks without treatment</td>
<td valign="top" align="left" rowspan="1" colspan="1">Hainsworth et al
<xref rid="b168-cia-10-157" ref-type="bibr">168</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">74 (50–88)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase II, 41 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First line 75%
<break></break>
Second line 25%</td>
<td valign="top" align="left" rowspan="1" colspan="1">ORR 36%
<break></break>
TTP 7 months
<break></break>
OS 13 months</td>
<td valign="top" align="left" rowspan="1" colspan="1">Severe neutropenia 0.4%
<break></break>
Grade 3/4 fatigue 20%</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">36 mg/m
<sup>2</sup>
per week</td>
<td valign="top" align="left" rowspan="1" colspan="1">D’hondt et al
<xref rid="b169-cia-10-157" ref-type="bibr">169</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">Frail and elderly patients (≥70 years)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase II, 47 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">Median: 2 prior chemotherapy regimens</td>
<td valign="top" align="left" rowspan="1" colspan="1">ORR 37%</td>
<td valign="top" align="left" rowspan="1" colspan="1">Febrile neutropenia 8.5%
<break></break>
Grade 3 neurotoxicity 2%</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">36 mg/m
<sup>2</sup>
per week (starting dose of 26 mg/m
<sup>2</sup>
and dose escalating if no toxicity is advised)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Hurria et al
<xref rid="b170-cia-10-157" ref-type="bibr">170</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">75 (66–84)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase I, 20 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">Prostate, lung, and breast (50%) cancer</td>
<td valign="top" align="left" rowspan="1" colspan="1"></td>
<td valign="top" align="left" rowspan="1" colspan="1">≥ Grade 3 58%
<break></break>
≥ Hematologic grade 3 16%
<break></break>
≥ Non-hematologic grade 3 53%</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Eribulin</td>
<td valign="top" align="left" rowspan="1" colspan="1">1.4 mg/m
<sup>2</sup>
on days 1 and 8 of a 21-day cycle</td>
<td valign="top" align="left" rowspan="1" colspan="1">Muss et al
<xref rid="b171-cia-10-157" ref-type="bibr">171</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">≥70 years, 79 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">Exploratory analysis from two Phase II studies and one Phase III randomized study, 827 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">Heavily pretreated MBC</td>
<td valign="top" align="left" rowspan="1" colspan="1">OS 12.5 months
<break></break>
PFS 4.0 months
<break></break>
ORR 10.1%
<break></break>
CBR 21.5%</td>
<td valign="top" align="left" rowspan="1" colspan="1">No overall effect of age on AEs</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="tfn3-cia-10-157">
<p>
<bold>Abbreviations:</bold>
AEs, adverse events; ORR, objective response rate; PFS, progression-free survival; OS, overall survival; TTP, time to progression; PR, partial response; SD, stable disease; CBR, clinical benefit rate; MBC, metastatic breast cancer.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="t3-cia-10-157" position="float">
<label>Table 3</label>
<caption>
<p>Comparison of chemotherapy regimens</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th valign="top" align="left" rowspan="1" colspan="1">Chemotherapy regimen</th>
<th valign="top" align="left" rowspan="1" colspan="1">Dosage</th>
<th valign="top" align="left" rowspan="1" colspan="1">Reference</th>
<th valign="top" align="left" rowspan="1" colspan="1">Age, median and range (years)</th>
<th valign="top" align="left" rowspan="1" colspan="1">Study design and population</th>
<th valign="top" align="left" rowspan="1" colspan="1">Line</th>
<th valign="top" align="left" rowspan="1" colspan="1">Efficacy</th>
<th valign="top" align="left" rowspan="1" colspan="1">Toxicity</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">PLD versus capecitabine</td>
<td valign="top" align="left" rowspan="1" colspan="1">6 cycles of PLD (45 mg/m
<sup>2</sup>
every 4 weeks) or 8 cycles of capecitabine (1,000 mg/m
<sup>2</sup>
twice daily, days 1–14 every 3 weeks)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Smorenburg et al
<xref rid="b160-cia-10-157" ref-type="bibr">160</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">75 (65–86)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Multicenter, randomized, Phase III, 78 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First line</td>
<td valign="top" align="left" rowspan="1" colspan="1">PFS 5.6 versus 7.7 months,
<italic>P</italic>
=0.11 OS 13.8 versus 16.8 months,
<italic>P</italic>
=0.59</td>
<td valign="top" align="left" rowspan="1" colspan="1">Comparable grade 3 AEs, no grade 4 AEs</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Epirubicin versus gemcitabine</td>
<td valign="top" align="left" rowspan="1" colspan="1">Epirubicin 35 mg/m
<sup>2</sup>
or gemcitabine 1,200 mg/m
<sup>2</sup>
on days 1, 8, and 15 of a 28-day cycle</td>
<td valign="top" align="left" rowspan="1" colspan="1">Feher et al
<xref rid="b206-cia-10-157" ref-type="bibr">206</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">68 (59–91)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Multicenter, randomized, Phase III, 397 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First line</td>
<td valign="top" align="left" rowspan="1" colspan="1">Superiority of epirubicin TTP 6.1 versus 3.4 months,
<italic>P</italic>
=0.0001; OS 19.1 versus 11.8,
<italic>P</italic>
=0.0004; Independently assessed RR 40.3% versus 16.4%,
<italic>P</italic>
<0.001, 186 and 183 evaluable patients)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Both well tolerated</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Ixabepilone plus capecitabine versus capecitabine</td>
<td valign="top" align="left" rowspan="1" colspan="1">Ixabepilone 40 mg/m
<sup>2</sup>
every 3 weeks + oral capecitabine (1,000 mg/m
<sup>2</sup>
twice each day), or capecitabine alone (1,250 mg/m
<sup>2</sup>
twice each day)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Vahdat et al
<xref rid="b207-cia-10-157" ref-type="bibr">207</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">≥65</td>
<td valign="top" align="left" rowspan="1" colspan="1">Retrospective analysis, 251 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">Anthracycline and taxane pretreated</td>
<td valign="top" align="left" rowspan="1" colspan="1">PFS 5.5 versus 3.9 months
<break></break>
ORR 37% versus 19%
<break></break>
OS 13.9 versus 12.2 months</td>
<td valign="top" align="left" rowspan="1" colspan="1">Febrile neutropenia 10% (ixabepilone + capecitabine)</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Paclitaxel versus docetaxel</td>
<td valign="top" align="left" rowspan="1" colspan="1">Weekly paclitaxel 80 mg/m
<sup>2</sup>
or weekly docetaxel 36 mg/m
<sup>2</sup>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">Beuselinck et al
<xref rid="b208-cia-10-157" ref-type="bibr">208</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">Elderly or frail patients 63.7 (31–84)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Randomized, multicentric, Phase II, 70 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First line 17%
<break></break>
Second line 49%
<break></break>
Third line or more 34%</td>
<td valign="top" align="left" rowspan="1" colspan="1">PR 48% versus 38%, TTP 21.1 weeks versus 12.7 weeks
<break></break>
OS 55.7 weeks versus 32 weeks</td>
<td valign="top" align="left" rowspan="1" colspan="1">More anemia and neurotoxicity for paclitaxel and more edema and fatigue for docetaxel</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="tfn4-cia-10-157">
<p>
<bold>Abbreviations:</bold>
ORR, objective response rate; PFS, progression-free survival; OS, overall survival; TTP, time to progression; PR, partial response; SD, stable disease; PLD, pegylated liposomal doxorubicin.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="t4-cia-10-157" position="float">
<label>Table 4</label>
<caption>
<p>Polychemotherapy regimens</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th valign="top" align="left" rowspan="1" colspan="1">Chemotherapy regimens</th>
<th valign="top" align="left" rowspan="1" colspan="1">Dosage</th>
<th valign="top" align="left" rowspan="1" colspan="1">References</th>
<th valign="top" align="left" rowspan="1" colspan="1">Age, median and range (years)</th>
<th valign="top" align="left" rowspan="1" colspan="1">Study design and population</th>
<th valign="top" align="left" rowspan="1" colspan="1">Line</th>
<th valign="top" align="left" rowspan="1" colspan="1">Efficacy</th>
<th valign="top" align="left" rowspan="1" colspan="1">Toxicity</th>
</tr>
</thead>
<tbody>
<tr>
<td rowspan="3" valign="top" align="left" colspan="1">Gemcitabine and vinorelbine</td>
<td valign="top" align="left" rowspan="1" colspan="1">Vinorelbine 25 mg/m
<sup>2</sup>
IV and gemcitabine 1,000 mg/m
<sup>2</sup>
IV on days 1 and 8 every 3 weeks</td>
<td valign="top" align="left" rowspan="1" colspan="1">Dinota et al
<xref rid="b209-cia-10-157" ref-type="bibr">209</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">69 (65–87)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase II, 34 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First line</td>
<td valign="top" align="left" rowspan="1" colspan="1">ORR 53%</td>
<td valign="top" align="left" rowspan="1" colspan="1">Grade 3/4 neutropenia 20%</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Vinorelbine 25 mg/m
<sup>2</sup>
plus gemcitabine 1,000 mg/m
<sup>2</sup>
on days 1 and 8, every 3 weeks</td>
<td valign="top" align="left" rowspan="1" colspan="1">Basso et al
<xref rid="b210-cia-10-157" ref-type="bibr">210</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">74 (70–82)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase II prematurely terminated for poor RR, 12 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First line</td>
<td valign="top" align="left" rowspan="1" colspan="1">ORR 11.1%
<break></break>
TTP 3 months</td>
<td valign="top" align="left" rowspan="1" colspan="1">Grade 3 neutropenia 25%
<break></break>
Grade 3 anemia and grade 3 GI toxicity 25%</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Gemcitabine 1,000 mg/m
<sup>2</sup>
and vinorelbine 25 mg/m
<sup>2</sup>
on days 1 and 8 every 3 weeks for a maximum of 6 cycles</td>
<td valign="top" align="left" rowspan="1" colspan="1">Dong et al
<xref rid="b172-cia-10-157" ref-type="bibr">172</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">73 (65–84)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase II, 51 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First line (54.9%)</td>
<td valign="top" align="left" rowspan="1" colspan="1">RR 33.3%
<break></break>
PFS 6.2 months
<break></break>
OS 17 months</td>
<td valign="top" align="left" rowspan="1" colspan="1">Febrile neutropenia 4% One toxic death because of GI hemorrhage</td>
</tr>
<tr>
<td rowspan="2" valign="top" align="left" colspan="1">PLD plus vinorelbine</td>
<td valign="top" align="left" rowspan="1" colspan="1">PLD 40 mg/m
<sup>2</sup>
plus vinorelbine 25 mg/m
<sup>2</sup>
IV on day 1 and oral vinorelbine 60 mg/m
<sup>2</sup>
on day 15</td>
<td valign="top" align="left" rowspan="1" colspan="1">Addeo et al
<xref rid="b211-cia-10-157" ref-type="bibr">211</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">71 (65–82)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Phase II, 34 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First line</td>
<td valign="top" align="left" rowspan="1" colspan="1">ORR 50%
<break></break>
OS 13 months
<break></break>
TTP 8 months</td>
<td valign="top" align="left" rowspan="1" colspan="1">Neutropenia grade 3/4 26% Febrile neutropenia 8.8%</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">PLD 40 mg/m
<sup>2</sup>
IV on day 1 and vinorelbine 30 mg/m
<sup>2</sup>
IV on days 1 and 15 every 4 weeks</td>
<td valign="top" align="left" rowspan="1" colspan="1">Mlineritsch et al
<xref rid="b212-cia-10-157" ref-type="bibr">212</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">68 (60–82)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Multicenter, Phase II, 42 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First line</td>
<td valign="top" align="left" rowspan="1" colspan="1">ORR 36%
<break></break>
TTP 4 months
<break></break>
OS 24 months</td>
<td valign="top" align="left" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td valign="top" align="left" rowspan="1" colspan="1">Oral capecitabine and vinorelbine</td>
<td valign="top" align="left" rowspan="1" colspan="1">6 cycles: capecitabine 750 mg/m
<sup>2</sup>
bid, days 1–14 every 21 days Vinorelbine 45 mg/m
<sup>2</sup>
, days 1 and 8
<break></break>
Dose escalation after 3 cycles depending on tolerance (capecitabine 1,000 mg/m
<sup>2</sup>
bid, days 1–14 and vinorelbine 60 mg/m
<sup>2</sup>
, days 1 and 8)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Rousseau et al
<xref rid="b173-cia-10-157" ref-type="bibr">173</xref>
</td>
<td valign="top" align="left" rowspan="1" colspan="1">75.5 (69–86)</td>
<td valign="top" align="left" rowspan="1" colspan="1">Multicenter, Phase II trial, 80 patients</td>
<td valign="top" align="left" rowspan="1" colspan="1">First line</td>
<td valign="top" align="left" rowspan="1" colspan="1">ORR 8.6% 1-year PFS 9.8%
<break></break>
1-year OS 54.9%</td>
<td valign="top" align="left" rowspan="1" colspan="1">Febrile neutropenia 1.3% grade 3/4 hematological toxicity: 17.9%
<break></break>
Grade 3/4 GI toxicity 7.7%</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="tfn5-cia-10-157">
<p>
<bold>Abbreviations:</bold>
ORR, objective response rate; PFS, progression-free survival; OS, overall survival; TTP, time to progression; PLD, pegylated liposomal doxorubicin; RR, response rate; GI, gastrointestinal; IV, intravenous; bid, twice daily.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
<affiliations>
<list>
<country>
<li>France</li>
</country>
<region>
<li>Auvergne-Rhône-Alpes</li>
<li>Rhône-Alpes</li>
</region>
<settlement>
<li>Lyon</li>
<li>Saint-Étienne</li>
</settlement>
</list>
<tree>
<country name="France">
<noRegion>
<name sortKey="Le Saux, Olivia" sort="Le Saux, Olivia" uniqKey="Le Saux O" first="Olivia" last="Le Saux">Olivia Le Saux</name>
</noRegion>
<name sortKey="Bonin, Olivier" sort="Bonin, Olivier" uniqKey="Bonin O" first="Olivier" last="Bonin">Olivier Bonin</name>
<name sortKey="Bonnefoy, Marc" sort="Bonnefoy, Marc" uniqKey="Bonnefoy M" first="Marc" last="Bonnefoy">Marc Bonnefoy</name>
<name sortKey="Bonnefoy, Marc" sort="Bonnefoy, Marc" uniqKey="Bonnefoy M" first="Marc" last="Bonnefoy">Marc Bonnefoy</name>
<name sortKey="Bruyas, Amandine" sort="Bruyas, Amandine" uniqKey="Bruyas A" first="Amandine" last="Bruyas">Amandine Bruyas</name>
<name sortKey="Bruyas, Amandine" sort="Bruyas, Amandine" uniqKey="Bruyas A" first="Amandine" last="Bruyas">Amandine Bruyas</name>
<name sortKey="Falandry, Claire" sort="Falandry, Claire" uniqKey="Falandry C" first="Claire" last="Falandry">Claire Falandry</name>
<name sortKey="Falandry, Claire" sort="Falandry, Claire" uniqKey="Falandry C" first="Claire" last="Falandry">Claire Falandry</name>
<name sortKey="Freyer, Gilles" sort="Freyer, Gilles" uniqKey="Freyer G" first="Gilles" last="Freyer">Gilles Freyer</name>
<name sortKey="Freyer, Gilles" sort="Freyer, Gilles" uniqKey="Freyer G" first="Gilles" last="Freyer">Gilles Freyer</name>
<name sortKey="Ripamonti, Bertrand" sort="Ripamonti, Bertrand" uniqKey="Ripamonti B" first="Bertrand" last="Ripamonti">Bertrand Ripamonti</name>
</country>
</tree>
</affiliations>
</record>

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