A phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory mantle cell lymphoma
Identifieur interne : 009868 ( Main/Merge ); précédent : 009867; suivant : 009869A phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory mantle cell lymphoma
Auteurs : F. Morschhauser [France] ; J. F. Seymour [Australie] ; H. C. Kluin-Nelemans [Pays-Bas] ; A. Grigg [Australie] ; M. Wolf [Allemagne] ; M. Pfreundschuh [Allemagne] ; H. Tilly [France] ; J. Raemaekers [Pays-Bas] ; M. B. Van T Veer [Pays-Bas] ; N. Milpied [France] ; G. Cartron [France] ; A. Pezzutto [Allemagne] ; A. Spencer [Australie] ; F. Reyes [France] ; M. Dreyling [Allemagne]Source :
- Annals of oncology [ 0923-7534 ] ; 2008.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
Abstract
Background: Protein kinase C beta (PKCβ), a pivotal enzyme in B-cell signaling and survival, is overexpressed in most cases of mantle cell lymphoma (MCL). Activation of P13K/AKT pathway is involved in pathogenesis of MCL. Enzastaurin, an oral serine/threonine kinase inhibitor, suppresses signaling through PKCβ/P13K/AKT pathways, induces apoptosis, reduces proliferation, and suppresses tumor-induced angiogenesis. Patients and methods: Patients with relapsed/refractory MCL, and no more than four regimens of prior therapy, received 500 mg enzastaurin, orally, once daily. Results: Sixty patients, median age 66 years (range 45-85), Eastern Cooperative Oncology Group performance status of zero to two (48% had baseline International Prognostic Index of 3-5), were enrolled. Most patients had prior CHOP-like chemotherapy and/or rituximab (median = 2 regimens). No drug-related deaths occurred. There was one case each of grade 3 anemia, diarrhea, dyspnea, vomiting, hypotension, and syncope. Fatigue was the most common toxicity. Although no objective tumor responses occurred, 22 patients (37%, 95% Cl 25% to 49%) were free from progression (FFP) for ≥3 cycles (one cycle = 28 days); 6 of 22 were FFP for >6 months. Two patients remain on treatment and FFP at >23 months. Conclusion: Freedom from progression for >6 months in six patients and a favorable toxicity profile with minimal hematological toxicity indicate that enzastaurin warrants evaluation as maintenance therapy and combination chemotherapy in MCL.
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Pascal:08-0139123Le document en format XML
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<s2>Creteil</s2>
<s3>FRA</s3>
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<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Créteil</settlement>
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<s3>DEU</s3>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>B cell neoplasm</term>
<term>B-Lymphocyte</term>
<term>Enzastaurin</term>
<term>Human</term>
<term>Inhibitor</term>
<term>Mantle cell lymphoma</term>
<term>Phase II trial</term>
<term>Protein kinase C</term>
<term>Protein kinase Cβ</term>
<term>Relapse</term>
<term>Treatment</term>
<term>Treatment resistance</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Homme</term>
<term>Essai clinique phase II</term>
<term>Traitement</term>
<term>Enzastaurine</term>
<term>Protein kinase C</term>
<term>Inhibiteur</term>
<term>Récidive</term>
<term>Résistance traitement</term>
<term>Lymphome centrocytique</term>
<term>Lymphocyte B</term>
<term>Protein kinase Cβ</term>
<term>Hémopathie lymphoïde B</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Background: Protein kinase C beta (PKCβ), a pivotal enzyme in B-cell signaling and survival, is overexpressed in most cases of mantle cell lymphoma (MCL). Activation of P13K/AKT pathway is involved in pathogenesis of MCL. Enzastaurin, an oral serine/threonine kinase inhibitor, suppresses signaling through PKCβ/P13K/AKT pathways, induces apoptosis, reduces proliferation, and suppresses tumor-induced angiogenesis. Patients and methods: Patients with relapsed/refractory MCL, and no more than four regimens of prior therapy, received 500 mg enzastaurin, orally, once daily. Results: Sixty patients, median age 66 years (range 45-85), Eastern Cooperative Oncology Group performance status of zero to two (48% had baseline International Prognostic Index of 3-5), were enrolled. Most patients had prior CHOP-like chemotherapy and/or rituximab (median = 2 regimens). No drug-related deaths occurred. There was one case each of grade 3 anemia, diarrhea, dyspnea, vomiting, hypotension, and syncope. Fatigue was the most common toxicity. Although no objective tumor responses occurred, 22 patients (37%, 95% Cl 25% to 49%) were free from progression (FFP) for ≥3 cycles (one cycle = 28 days); 6 of 22 were FFP for >6 months. Two patients remain on treatment and FFP at >23 months. Conclusion: Freedom from progression for >6 months in six patients and a favorable toxicity profile with minimal hematological toxicity indicate that enzastaurin warrants evaluation as maintenance therapy and combination chemotherapy in MCL.</div>
</front>
</TEI>
<affiliations><list><country><li>Allemagne</li>
<li>Australie</li>
<li>France</li>
<li>Pays-Bas</li>
</country>
<region><li>Berlin</li>
<li>Centre-Val de Loire</li>
<li>District de Kassel</li>
<li>Groningue (province)</li>
<li>Gueldre</li>
<li>Haute-Normandie</li>
<li>Hauts-de-France</li>
<li>Hesse (Land)</li>
<li>Hollande-Méridionale</li>
<li>Nord-Pas-de-Calais</li>
<li>Pays de la Loire</li>
<li>Région Centre</li>
<li>Région Normandie</li>
<li>Victoria (État)</li>
<li>Île-de-France</li>
</region>
<settlement><li>Berlin</li>
<li>Cassel (Hesse)</li>
<li>Créteil</li>
<li>Groningue (ville)</li>
<li>Lille</li>
<li>Melbourne</li>
<li>Nantes</li>
<li>Nimègue</li>
<li>Rotterdam</li>
<li>Rouen</li>
<li>Tours</li>
</settlement>
<orgName><li>Université de Groningue</li>
<li>Université de Melbourne</li>
</orgName>
</list>
<tree><country name="France"><region name="Hauts-de-France"><name sortKey="Morschhauser, F" sort="Morschhauser, F" uniqKey="Morschhauser F" first="F." last="Morschhauser">F. Morschhauser</name>
</region>
<name sortKey="Cartron, G" sort="Cartron, G" uniqKey="Cartron G" first="G." last="Cartron">G. Cartron</name>
<name sortKey="Milpied, N" sort="Milpied, N" uniqKey="Milpied N" first="N." last="Milpied">N. Milpied</name>
<name sortKey="Reyes, F" sort="Reyes, F" uniqKey="Reyes F" first="F." last="Reyes">F. Reyes</name>
<name sortKey="Tilly, H" sort="Tilly, H" uniqKey="Tilly H" first="H." last="Tilly">H. Tilly</name>
</country>
<country name="Australie"><region name="Victoria (État)"><name sortKey="Seymour, J F" sort="Seymour, J F" uniqKey="Seymour J" first="J. F." last="Seymour">J. F. Seymour</name>
</region>
<name sortKey="Grigg, A" sort="Grigg, A" uniqKey="Grigg A" first="A." last="Grigg">A. Grigg</name>
<name sortKey="Spencer, A" sort="Spencer, A" uniqKey="Spencer A" first="A." last="Spencer">A. Spencer</name>
</country>
<country name="Pays-Bas"><region name="Groningue (province)"><name sortKey="Kluin Nelemans, H C" sort="Kluin Nelemans, H C" uniqKey="Kluin Nelemans H" first="H. C." last="Kluin-Nelemans">H. C. Kluin-Nelemans</name>
</region>
<name sortKey="Raemaekers, J" sort="Raemaekers, J" uniqKey="Raemaekers J" first="J." last="Raemaekers">J. Raemaekers</name>
<name sortKey="Van T Veer, M B" sort="Van T Veer, M B" uniqKey="Van T Veer M" first="M. B." last="Van T Veer">M. B. Van T Veer</name>
</country>
<country name="Allemagne"><region name="Hesse (Land)"><name sortKey="Wolf, M" sort="Wolf, M" uniqKey="Wolf M" first="M." last="Wolf">M. Wolf</name>
</region>
<name sortKey="Dreyling, M" sort="Dreyling, M" uniqKey="Dreyling M" first="M." last="Dreyling">M. Dreyling</name>
<name sortKey="Pezzutto, A" sort="Pezzutto, A" uniqKey="Pezzutto A" first="A." last="Pezzutto">A. Pezzutto</name>
<name sortKey="Pfreundschuh, M" sort="Pfreundschuh, M" uniqKey="Pfreundschuh M" first="M." last="Pfreundschuh">M. Pfreundschuh</name>
</country>
</tree>
</affiliations>
</record>
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