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

Autor:	Morschhauser F; Hematology, Hopital C. Huriez Centre Hospitalier Universitaire, Lille, France. f-morschhauser@chru-lille.fr, Seymour JF, Kluin-Nelemans HC, Grigg A, Wolf M, Pfreundschuh M, Tilly H, Raemaekers J, van 't Veer MB, Milpied N, Cartron G, Pezzutto A, Spencer A, Reyes F, Dreyling M
Jazyk:	angličtina
Zdroj:	Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2008 Feb; Vol. 19 (2), pp. 247-53. Date of Electronic Publication: 2007 Sep 28.
DOI:	10.1093/annonc/mdm463
Abstrakt:	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 > or =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.
Databáze:	MEDLINE
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