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

摘要: textabstractBackground: Protein kinase C beta (PKCβ), a pivotal enzyme in B-cell signaling and survival, is overexpressed most cases of mantle cell lymphoma (MCL). Activation PI3K/AKT pathway involved pathogenesis MCL. Enzastaurin, an oral serine/threonine inhibitor, suppresses through PKCβ/PI3K/AKT pathways, induces apoptosis, reduces proliferation, tumor-induced angiogenesis. Patients methods: with relapsed/refractory MCL, no more than four regimens 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 zero to two (48% had baseline International Prognostic Index 3-5), were enrolled. Most patients CHOP-like chemotherapy and/or rituximab (median = 2 regimens). No drug-related deaths occurred. There was one case each grade 3 anemia, diarrhea, dyspnea, vomiting, hypotension, syncope. Fatigue the common toxicity. Although objective tumor responses occurred, 22 (37%, 95% CI 25% 49%) free from progression (FFP) for ≥3 cycles (one cycle 28 days); 6 FFP >6 months. Two remain on treatment at >23 Conclusion: Freedom months six favorable toxicity profile minimal hematological indicate that enzastaurin warrants evaluation as maintenance therapy combination