title: Open-label, single-arm, phase II study of enzastaurin in patients with follicular lymphoma.
abstract: This open-label, phase II study investigated whether enzastaurin, a protein kinase C-beta (PKCβ) inhibitor, had activity in patients with grade 1 or 2 follicular lymphoma (FL). Adults with grade 1 or 2 FL who had no more than one prior treatment received oral enzastaurin continuously for up to 3 years. Of the 66 patients who received enzastaurin, 53 were evaluable for response. Overall response rate (ORR, primary efficacy endpoint) was 26.4% (3.8% complete response). Median (95% confidence interval) progression-free survival, time to response, and duration of response were 18.1 (11.5-28.3), 4.9 (2.8-8.1), and 22.3 (8.8-not applicable) months, respectively. In patients with tumour tissue available for biomarker analysis, ORRs in low versus high PKCβ2 expression groups were 41.7% and 8.3%, respectively (P = 0.041). The most common, mainly low-grade drug-related adverse events were fatigue (25.8%), diarrhoea (25.8%), nausea (18.2%), and chromaturia (18.2%). Four (6.1%) patients had Grade 3 toxicity and one (1.5%) patient had Grade 4 toxicity. Enzastaurin demonstrated limited clinical activity in grade 1 or 2 FL. Patients with low PKCβ2 expression in tumours had higher ORR than those with high PKCβ2 expression. Enzastaurin was well tolerated with mostly grade 1 or 2 toxicities. Further studies may be warranted in select patient populations.
authors.affiliation: West Clinic, Memphis, TN, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Schwartzberg
authors.forename: Robert
authors.initials: R
authors.lastname: Hermann
authors.forename: Ian
authors.initials: I
authors.lastname: Flinn
authors.forename: Douglas
authors.initials: D
authors.lastname: Flora
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.forename: Oday
authors.initials: O
authors.lastname: Hamid
authors.forename: Peipei
authors.initials: P
authors.lastname: Shi
authors.forename: Boris K
authors.initials: BK
authors.lastname: Lin
authors.forename: Scott P
authors.initials: SP
authors.lastname: Myrand
authors.forename: Tuan S
authors.initials: TS
authors.lastname: Nguyen
authors.forename: Martin
authors.initials: M
authors.lastname: Dreyling
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D064546:Protein Kinase C beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D047428:Protein Kinase Inhibitors; D064546:Protein Kinase C beta; C504878:enzastaurin
keywords: PKCβ; enzastaurin; follicular lymphoma; indolent Non-Hodgkin lymphoma; phase II