A phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory mantle cell lymphoma.
Ann Oncol
; 19(2): 247-53, 2008 Feb.
Article
en En
| MEDLINE
| ID: mdl-17906297
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 ANDMETHODS:
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.
Buscar en Google
Banco de datos:
MEDLINE
Asunto principal:
Proteína Quinasa C
/
Linfoma de Células del Manto
/
Indoles
Tipo de estudio:
Prognostic_studies
Límite:
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Ann Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2008
Tipo del documento:
Article
País de afiliación:
Francia