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A phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory mantle cell lymphoma

Item Type:Article
Title:A phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory mantle cell lymphoma
Creators Name:Morschhauser, F. and Seymour, J.F. and Kluin-Nelemans, H.C. and Grigg, A. and Wolf, M. and Pfreundschuh, M. and Tilly, H. and Raemaekers, J. and van't Veer, M.B. and Milpied, N. and Cartron, G. and Pezzutto, A. and Spencer, A. and Reyes, F. and Dreyling, M.
Abstract:BACKGROUND: Protein kinase C beta (PKCbeta), a pivotal enzyme in B-cell signaling and survival, is overexpressed in most cases of mantle cell lymphoma (MCL). Activation of PI3K/AKT pathway is involved in pathogenesis of MCL. Enzastaurin, an oral serine/threonine kinase inhibitor, suppresses signaling through PKCbeta/PI3K/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% CI 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.
Keywords:Enzastaurin, Mantle cell lymphoma, PKCbeta inhibitor
Source:Annals of Oncology
ISSN:0923-7534
Publisher:Oxford University Press (U.K.)
Volume:19
Number:2
Page Range:247-253
Date:February 2008
Official Publication:https://doi.org/10.1093/annonc/mdm463
PubMed:View item in PubMed

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