PittsburghV1, Main, Merge, bibRecord, 007331

Fixed-dose capecitabine is feasible: results from a pharmacokinetic and pharmacogenetic study in metastatic breast cancer

Identifieur interne : 007331 ( Main/Merge ); précédent : 007330; suivant : 007332

Fixed-dose capecitabine is feasible: results from a pharmacokinetic and pharmacogenetic study in metastatic breast cancer

Auteurs : Michelle A. Rudek [États-Unis] ; Roisin M. Connolly [États-Unis] ; Janelle M. Hoskins [États-Unis] ; Elizabeth Garrett-Mayer [États-Unis] ; Stacie C. Jeter [États-Unis] ; Deborah K. Armstrong [États-Unis] ; John H. Fetting [États-Unis] ; Vered Stearns [États-Unis] ; Laurie A. Wright [États-Unis] ; MING ZHAO [États-Unis] ; Stanley P. Jr Watkins [États-Unis] ; Howard L. Mcleod [États-Unis] ; Nancy E. Davidson [États-Unis] ; Antonio C. Wolff [États-Unis]

Source :

Breast cancer research and treatment [ 0167-6806 ] ; 2013.

RBID : Pascal:13-0261989

Descripteurs français

Pascal (Inist)
- Capécitabine, Pharmacocinétique, Pharmacogénétique, Stade avancé, Métastase, Cancer du sein, Anticancéreux, Promédicament, Combinaison à dose fixe, Antipyrimidique.

English descriptors

KwdEn :
- Advanced stage, Antineoplastic agent, Breast cancer, Capecitabine, Metastasis, Pharmacogenetics, Pharmacokinetics, Prodrug.

Abstract

The pro-drug capecitabine is approved for treatment of anthracycline- and paclitaxel-resistant metastatic breast cancer. However, toxicity and large interpatient pharmacokinetic variability occur despite body surface area (BSA)-dosing. We hypothesized that a fixed-dose schedule would simplify dosing and provide an effective and safe alternative to BSA-based dosing. We conducted an open label, single-arm, two-stage study of oral capecitabine with fixed starting dose (3,000 mg total daily dose in two divided doses × 14 days q21 days) in patients with metastatic breast cancer. We correlated pharmacodynamic endpoints [e.g., efficacy (response) per RECIST and toxicity], adherence and pharmacokinetics/pharmacogenetics. Sample size of 45 patients was required to detect a 25 % response rate from null response rate of 10 % using a Simon two-stage design. Twenty-six patients were enrolled in the first-stage and 21 were evaluable after a median of four cycles of capecitabine. Two thirds of patients received either the same dose or a dose 500 mg lower than what would have been administered with a commonly used 2,000 mg/m² BSA-dosing schedule. Eight patients had stable disease but progressed after a median of seven cycles. Despite a clinical benefit rate of 19 %, no RECIST responses were observed following the first stage and the study was closed. Dose-reductions were required for grade 2 hand-foot syndrome (28 %) and vomiting (5 %). Adherence was similar when using both patient-reported and Medication Event Monitoring System methods. High interpatient variability was observed for capecitabine and metabolite pharmacokinetics, but was not attributed to observed pharmacogenetic or BSA differences. Single agent activity of capecitabine was modest in our patients with estrogen receptor-positive or -negative metastatic breast cancer and comparable to recent studies. BSA was not the main source of pharmacokinetic variability. Fixed-dose capecitabine is feasible, and simplifies dosing.

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Le document en format XML

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</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>University of North Carolina</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Davidson, Nancy E" sort="Davidson, Nancy E" uniqKey="Davidson N" first="Nancy E." last="Davidson">Nancy E. Davidson</name>
<affiliation wicri:level="1"><inist:fA14 i1="05"><s1>University of Pittsburgh Cancer Institute and UPMC Cancer Center</s1>
<s2>Pittsburgh, PA</s2>
<s3>USA</s3>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>University of Pittsburgh Cancer Institute and UPMC Cancer Center</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wolff, Antonio C" sort="Wolff, Antonio C" uniqKey="Wolff A" first="Antonio C." last="Wolff">Antonio C. Wolff</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 1650 Orleans Street, CRB1-1M52</s1>
<s2>Baltimore, MD 21231</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Baltimore, MD 21231</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Breast cancer research and treatment</title>
<title level="j" type="abbreviated">Breast cancer res. treat.</title>
<idno type="ISSN">0167-6806</idno>
<imprint><date when="2013">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Breast cancer research and treatment</title>
<title level="j" type="abbreviated">Breast cancer res. treat.</title>
<idno type="ISSN">0167-6806</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Advanced stage</term>
<term>Antineoplastic agent</term>
<term>Breast cancer</term>
<term>Capecitabine</term>
<term>Metastasis</term>
<term>Pharmacogenetics</term>
<term>Pharmacokinetics</term>
<term>Prodrug</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Capécitabine</term>
<term>Pharmacocinétique</term>
<term>Pharmacogénétique</term>
<term>Stade avancé</term>
<term>Métastase</term>
<term>Cancer du sein</term>
<term>Anticancéreux</term>
<term>Promédicament</term>
<term>Combinaison à dose fixe</term>
<term>Antipyrimidique</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">The pro-drug capecitabine is approved for treatment of anthracycline- and paclitaxel-resistant metastatic breast cancer. However, toxicity and large interpatient pharmacokinetic variability occur despite body surface area (BSA)-dosing. We hypothesized that a fixed-dose schedule would simplify dosing and provide an effective and safe alternative to BSA-based dosing. We conducted an open label, single-arm, two-stage study of oral capecitabine with fixed starting dose (3,000 mg total daily dose in two divided doses × 14 days q21 days) in patients with metastatic breast cancer. We correlated pharmacodynamic endpoints [e.g., efficacy (response) per RECIST and toxicity], adherence and pharmacokinetics/pharmacogenetics. Sample size of 45 patients was required to detect a 25 % response rate from null response rate of 10 % using a Simon two-stage design. Twenty-six patients were enrolled in the first-stage and 21 were evaluable after a median of four cycles of capecitabine. Two thirds of patients received either the same dose or a dose 500 mg lower than what would have been administered with a commonly used 2,000 mg/m<sup>2</sup>
 BSA-dosing schedule. Eight patients had stable disease but progressed after a median of seven cycles. Despite a clinical benefit rate of 19 %, no RECIST responses were observed following the first stage and the study was closed. Dose-reductions were required for grade 2 hand-foot syndrome (28 %) and vomiting (5 %). Adherence was similar when using both patient-reported and Medication Event Monitoring System methods. High interpatient variability was observed for capecitabine and metabolite pharmacokinetics, but was not attributed to observed pharmacogenetic or BSA differences. Single agent activity of capecitabine was modest in our patients with estrogen receptor-positive or -negative metastatic breast cancer and comparable to recent studies. BSA was not the main source of pharmacokinetic variability. Fixed-dose capecitabine is feasible, and simplifies dosing.</div>
</front>
</TEI>
<affiliations><list><country><li>États-Unis</li>
</country>
</list>
<tree><country name="États-Unis"><noRegion><name sortKey="Rudek, Michelle A" sort="Rudek, Michelle A" uniqKey="Rudek M" first="Michelle A." last="Rudek">Michelle A. Rudek</name>
</noRegion>
<name sortKey="Armstrong, Deborah K" sort="Armstrong, Deborah K" uniqKey="Armstrong D" first="Deborah K." last="Armstrong">Deborah K. Armstrong</name>
<name sortKey="Connolly, Roisin M" sort="Connolly, Roisin M" uniqKey="Connolly R" first="Roisin M." last="Connolly">Roisin M. Connolly</name>
<name sortKey="Davidson, Nancy E" sort="Davidson, Nancy E" uniqKey="Davidson N" first="Nancy E." last="Davidson">Nancy E. Davidson</name>
<name sortKey="Fetting, John H" sort="Fetting, John H" uniqKey="Fetting J" first="John H." last="Fetting">John H. Fetting</name>
<name sortKey="Garrett Mayer, Elizabeth" sort="Garrett Mayer, Elizabeth" uniqKey="Garrett Mayer E" first="Elizabeth" last="Garrett-Mayer">Elizabeth Garrett-Mayer</name>
<name sortKey="Hoskins, Janelle M" sort="Hoskins, Janelle M" uniqKey="Hoskins J" first="Janelle M." last="Hoskins">Janelle M. Hoskins</name>
<name sortKey="Jeter, Stacie C" sort="Jeter, Stacie C" uniqKey="Jeter S" first="Stacie C." last="Jeter">Stacie C. Jeter</name>
<name sortKey="Mcleod, Howard L" sort="Mcleod, Howard L" uniqKey="Mcleod H" first="Howard L." last="Mcleod">Howard L. Mcleod</name>
<name sortKey="Ming Zhao" sort="Ming Zhao" uniqKey="Ming Zhao" last="Ming Zhao">MING ZHAO</name>
<name sortKey="Stearns, Vered" sort="Stearns, Vered" uniqKey="Stearns V" first="Vered" last="Stearns">Vered Stearns</name>
<name sortKey="Watkins, Stanley P Jr" sort="Watkins, Stanley P Jr" uniqKey="Watkins S" first="Stanley P. Jr" last="Watkins">Stanley P. Jr Watkins</name>
<name sortKey="Wolff, Antonio C" sort="Wolff, Antonio C" uniqKey="Wolff A" first="Antonio C." last="Wolff">Antonio C. Wolff</name>
<name sortKey="Wright, Laurie A" sort="Wright, Laurie A" uniqKey="Wright L" first="Laurie A." last="Wright">Laurie A. Wright</name>
</country>
</tree>
</affiliations>
</record>

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Fixed-dose capecitabine is feasible: results from a pharmacokinetic and pharmacogenetic study in metastatic breast cancer

Fixed-dose capecitabine is feasible: results from a pharmacokinetic and pharmacogenetic study in metastatic breast cancer

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