Phase III Study of Enzastaurin Compared With Lomustine in the Treatment of Recurrent Intracranial Glioblastoma
Identifieur interne : 007639 ( Main/Exploration ); précédent : 007638; suivant : 007640Phase III Study of Enzastaurin Compared With Lomustine in the Treatment of Recurrent Intracranial Glioblastoma
Auteurs : Wolfgang Wick [Allemagne, États-Unis, Pays-Bas, France, Australie, Canada] ; Vinay K. Puduvalli ; Marc C. Chamberlain ; Martin J. Van Den Bent ; Antoine F. Carpentier ; Lawrence M. Cher ; Warren Mason ; Michael Weller ; SHENGYAN HONG ; Luna Musib ; Astra M. Liepa ; Donald E. Thornton ; Howard A. FineSource :
- Journal of clinical oncology [ 0732-183X ] ; 2010.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Purpose This phase III open-label study compared the efficacy and safety of enzastaurin versus lomustine in patients with recurrent glioblastoma (WHO grade 4). Patients and Methods Patients were randomly assigned 2:1 to receive 6-week cycles of enzastaurin 500 mg/d (1,125-mg loading dose, day 1) or lomustine (100 to 130 mg/m2, day 1). Assuming a 45% improvement in progression-free survival (PFS), 397 patients were required to provide 80% power to achieve statistical significance at a one-sided level of .025. Results Enrollment was terminated at 266 patients (enzastaurin, n = 174; lomustine, n = 92) after a planned interim analysis for futility. Patient characteristics were balanced between arms. Median PFS (1.5 v 1.6 months; hazard ratio [HR] = 1.28; 95% CI, 0.97 to 1.70), overall survival (6.6 v 7.1 months; HR = 1.20; 95% CI, 0.88 to 1.65), and 6-month PFS rate (P = .13) did not differ significantly between enzastaurin and lomustine, respectively. Stable disease occurred in 38.5% and 35.9% of patients and objective response occurred in 2.9% and 4.3% of patients, respectively. Time to deterioration of physical and functional well-being and symptoms did not differ between arms (HR = 1.12; P = .54). Four patients discontinued enzastaurin because of drug-related serious adverse events (AEs). Eleven patients treated with enzastaurin died on study (four because of AEs; one was drug-related). All four deaths that occurred in patients receiving lomustine were disease-related. Grade 3 to 4 hematologic toxicities were significantly higher with lomustine (46 events) than with enzastaurin (one event; P ≤ .001). Conclusion Enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma.
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Affiliations:
- Allemagne, Australie, Canada, France, Pays-Bas, États-Unis
- Ontario, Île-de-France
- Paris, Toronto
- Université de Toronto
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Lee Moffitt Cancer Center</s1><s2>Tampa, FL</s2><s3>USA</s3></inist:fA14><country>États-Unis</country><wicri:noRegion>H. Lee Moffitt Cancer Center</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Erasmus Medisch Centrum</s1><s2>Rotter-dam</s2><s3>NLD</s3></inist:fA14><country>Pays-Bas</country><wicri:noRegion>Erasmus Medisch Centrum</wicri:noRegion></affiliation><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Hopital Pitie Salpetriere</s1><s2>Paris</s2><s3>FRA</s3></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Austin Health</s1><s2>Victoria</s2><s3>AUS</s3></inist:fA14><country>Australie</country><wicri:noRegion>Austin Health</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="07"><s1>Princess Margaret Hospital and the University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Eli Lilly and Company</s1><s2>Indianapolis, IN</s2><s3>USA</s3></inist:fA14><country>États-Unis</country><wicri:noRegion>Eli Lilly and Company</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Neuro-Oncology Branch, National Cancer Institute</s1><s2>Bethesda, MD</s2><s3>USA</s3></inist:fA14><country>États-Unis</country><wicri:noRegion>Bethesda, MD</wicri:noRegion></affiliation></author><author><name sortKey="Puduvalli, Vinay K" sort="Puduvalli, Vinay K" uniqKey="Puduvalli V" first="Vinay K." last="Puduvalli">Vinay K. Puduvalli</name></author><author><name sortKey="Chamberlain, Marc C" sort="Chamberlain, Marc C" uniqKey="Chamberlain M" first="Marc C." last="Chamberlain">Marc C. Chamberlain</name></author><author><name sortKey="Van Den Bent, Martin J" sort="Van Den Bent, Martin J" uniqKey="Van Den Bent M" first="Martin J." last="Van Den Bent">Martin J. Van Den Bent</name></author><author><name sortKey="Carpentier, Antoine F" sort="Carpentier, Antoine F" uniqKey="Carpentier A" first="Antoine F." last="Carpentier">Antoine F. Carpentier</name></author><author><name sortKey="Cher, Lawrence M" sort="Cher, Lawrence M" uniqKey="Cher L" first="Lawrence M." last="Cher">Lawrence M. Cher</name></author><author><name sortKey="Mason, Warren" sort="Mason, Warren" uniqKey="Mason W" first="Warren" last="Mason">Warren Mason</name></author><author><name sortKey="Weller, Michael" sort="Weller, Michael" uniqKey="Weller M" first="Michael" last="Weller">Michael Weller</name></author><author><name sortKey="Shengyan Hong" sort="Shengyan Hong" uniqKey="Shengyan Hong" last="Shengyan Hong">SHENGYAN HONG</name></author><author><name sortKey="Musib, Luna" sort="Musib, Luna" uniqKey="Musib L" first="Luna" last="Musib">Luna Musib</name></author><author><name sortKey="Liepa, Astra M" sort="Liepa, Astra M" uniqKey="Liepa A" first="Astra M." last="Liepa">Astra M. Liepa</name></author><author><name sortKey="Thornton, Donald E" sort="Thornton, Donald E" uniqKey="Thornton D" first="Donald E." last="Thornton">Donald E. Thornton</name></author><author><name sortKey="Fine, Howard A" sort="Fine, Howard A" uniqKey="Fine H" first="Howard A." last="Fine">Howard A. Fine</name></author></analytic><series><title level="j" type="main">Journal of clinical oncology</title><title level="j" type="abbreviated">J. clin. oncol.</title><idno type="ISSN">0732-183X</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of clinical oncology</title><title level="j" type="abbreviated">J. clin. oncol.</title><idno type="ISSN">0732-183X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antineoplastic agent</term><term>Cancerology</term><term>Comparative study</term><term>Enzastaurin</term><term>Glioblastoma</term><term>Intracranial</term><term>Lomustine</term><term>Phase III trial</term><term>Relapse</term><term>Treatment</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Essai clinique phase III</term><term>Traitement</term><term>Etude comparative</term><term>Enzastaurine</term><term>Récidive</term><term>Intracrânien</term><term>Lomustine</term><term>Cancérologie</term><term>Glioblastome</term><term>Anticancéreux</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Purpose This phase III open-label study compared the efficacy and safety of enzastaurin versus lomustine in patients with recurrent glioblastoma (WHO grade 4). Patients and Methods Patients were randomly assigned 2:1 to receive 6-week cycles of enzastaurin 500 mg/d (1,125-mg loading dose, day 1) or lomustine (100 to 130 mg/m<sup>2</sup>, day 1). Assuming a 45% improvement in progression-free survival (PFS), 397 patients were required to provide 80% power to achieve statistical significance at a one-sided level of .025. Results Enrollment was terminated at 266 patients (enzastaurin, n = 174; lomustine, n = 92) after a planned interim analysis for futility. Patient characteristics were balanced between arms. Median PFS (1.5 v 1.6 months; hazard ratio [HR] = 1.28; 95% CI, 0.97 to 1.70), overall survival (6.6 v 7.1 months; HR = 1.20; 95% CI, 0.88 to 1.65), and 6-month PFS rate (P = .13) did not differ significantly between enzastaurin and lomustine, respectively. Stable disease occurred in 38.5% and 35.9% of patients and objective response occurred in 2.9% and 4.3% of patients, respectively. Time to deterioration of physical and functional well-being and symptoms did not differ between arms (HR = 1.12; P = .54). Four patients discontinued enzastaurin because of drug-related serious adverse events (AEs). Eleven patients treated with enzastaurin died on study (four because of AEs; one was drug-related). All four deaths that occurred in patients receiving lomustine were disease-related. Grade 3 to 4 hematologic toxicities were significantly higher with lomustine (46 events) than with enzastaurin (one event; P ≤ .001). Conclusion Enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>Canada</li><li>France</li><li>Pays-Bas</li><li>États-Unis</li></country><region><li>Ontario</li><li>Île-de-France</li></region><settlement><li>Paris</li><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><noCountry><name sortKey="Carpentier, Antoine F" sort="Carpentier, Antoine F" uniqKey="Carpentier A" first="Antoine F." last="Carpentier">Antoine F. Carpentier</name><name sortKey="Chamberlain, Marc C" sort="Chamberlain, Marc C" uniqKey="Chamberlain M" first="Marc C." last="Chamberlain">Marc C. Chamberlain</name><name sortKey="Cher, Lawrence M" sort="Cher, Lawrence M" uniqKey="Cher L" first="Lawrence M." last="Cher">Lawrence M. Cher</name><name sortKey="Fine, Howard A" sort="Fine, Howard A" uniqKey="Fine H" first="Howard A." last="Fine">Howard A. Fine</name><name sortKey="Liepa, Astra M" sort="Liepa, Astra M" uniqKey="Liepa A" first="Astra M." last="Liepa">Astra M. Liepa</name><name sortKey="Mason, Warren" sort="Mason, Warren" uniqKey="Mason W" first="Warren" last="Mason">Warren Mason</name><name sortKey="Musib, Luna" sort="Musib, Luna" uniqKey="Musib L" first="Luna" last="Musib">Luna Musib</name><name sortKey="Puduvalli, Vinay K" sort="Puduvalli, Vinay K" uniqKey="Puduvalli V" first="Vinay K." last="Puduvalli">Vinay K. Puduvalli</name><name sortKey="Shengyan Hong" sort="Shengyan Hong" uniqKey="Shengyan Hong" last="Shengyan Hong">SHENGYAN HONG</name><name sortKey="Thornton, Donald E" sort="Thornton, Donald E" uniqKey="Thornton D" first="Donald E." last="Thornton">Donald E. Thornton</name><name sortKey="Van Den Bent, Martin J" sort="Van Den Bent, Martin J" uniqKey="Van Den Bent M" first="Martin J." last="Van Den Bent">Martin J. Van Den Bent</name><name sortKey="Weller, Michael" sort="Weller, Michael" uniqKey="Weller M" first="Michael" last="Weller">Michael Weller</name></noCountry><country name="Allemagne"><noRegion><name sortKey="Wick, Wolfgang" sort="Wick, Wolfgang" uniqKey="Wick W" first="Wolfgang" last="Wick">Wolfgang Wick</name></noRegion></country><country name="États-Unis"><noRegion><name sortKey="Wick, Wolfgang" sort="Wick, Wolfgang" uniqKey="Wick W" first="Wolfgang" last="Wick">Wolfgang Wick</name></noRegion><name sortKey="Wick, Wolfgang" sort="Wick, Wolfgang" uniqKey="Wick W" first="Wolfgang" last="Wick">Wolfgang Wick</name><name sortKey="Wick, Wolfgang" sort="Wick, Wolfgang" uniqKey="Wick W" first="Wolfgang" last="Wick">Wolfgang Wick</name><name sortKey="Wick, Wolfgang" sort="Wick, Wolfgang" uniqKey="Wick W" first="Wolfgang" last="Wick">Wolfgang Wick</name></country><country name="Pays-Bas"><noRegion><name sortKey="Wick, Wolfgang" sort="Wick, Wolfgang" uniqKey="Wick W" first="Wolfgang" last="Wick">Wolfgang Wick</name></noRegion></country><country name="France"><region name="Île-de-France"><name sortKey="Wick, Wolfgang" sort="Wick, Wolfgang" uniqKey="Wick W" first="Wolfgang" last="Wick">Wolfgang Wick</name></region></country><country name="Australie"><noRegion><name sortKey="Wick, Wolfgang" sort="Wick, Wolfgang" uniqKey="Wick W" first="Wolfgang" last="Wick">Wolfgang Wick</name></noRegion></country><country name="Canada"><region name="Ontario"><name sortKey="Wick, Wolfgang" sort="Wick, Wolfgang" uniqKey="Wick W" first="Wolfgang" last="Wick">Wolfgang Wick</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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