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

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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., Seymour, J.F., Kluin-Nelemans, H.C., Grigg, A., Wolf, M., Pfreundschuh, M., Tilly, H., Raemaekers, J., van't Veer, M.B., Milpied, N., Cartron, G., Pezzutto, A., Spencer, A., 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
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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