A phase I/II study of bortezomib plus CHOP every 2 weeks (CHOP-14) in patients with advanced-stage diffuse large B-cell lymphomas
Open Access
- 1 January 2012
- journal article
- Published by The Korean Society of Hematology in The Korean Journal of Hematology
- Vol. 47 (1), 53-59
- https://doi.org/10.5045/kjh.2012.47.1.53
Abstract
Bortezomib targets molecular dysregulation of nuclear factor-κB activation and cell cycle control, which are characteristic features of diffuse large B-cell lymphoma (DLBCL). We evaluated the safety and efficacy of bortezomib treatment with dose-dense cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) every 2 weeks (CHOP-14). Untreated DLBCL patients were enrolled. A phase I dose-escalation study with 1.0, 1.3, and 1.6 mg/m2 bortezomib administration on day 1 and 4 in addition to the CHOP-14 regimen was performed to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT). Lenograstim 5 µg/kg/d was administered on day 4-13. The bortezomib dose from the phase I study was used in the phase II study. Nine and 37 patients were enrolled in the phase I and phase II studies, respectively. The analysis of the phase II results (40 patients) included data of the 3 patients in the last MTD dose cohort of the phase I trial. During the phase I trial, no DLT was observed at any bortezomib dose; therefore, the recommended dose was 1.6 mg/m2. In phase II, the overall response rate was 95% (complete response: 80%; partial response: 15%). Nine out of the 40 patients showed grade 3 sensory neuropathy, and 22 required at least 1 dose reduction. Three patients could not complete the intended 6 cycles of treatment because of severe neuropathy. Bortezomib plus CHOP-14 was highly effective for the treatment of untreated DLBCL patients, but in many cases, dose or schedule modification was required to reduce neurotoxicity.Keywords
This publication has 27 references indexed in Scilit:
- Novel disease targets and management approaches for diffuse large B-cell lymphomaLeukemia & Lymphoma, 2010
- Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphomaBlood, 2009
- Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literatureBlood, 2008
- Phase I study of proteasome inhibitor bortezomib plus CHOP in patients with advanced, aggressive T-cell or NK/T-cell lymphomaAnnals of Oncology, 2008
- Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON)Blood, 2006
- Gain of 1q21 in multiple myeloma: from bad to worse?Blood, 2006
- State-of-the-Art Therapeutics: Diffuse Large B-Cell LymphomaJournal of Clinical Oncology, 2005
- Long-Term Results of the R-CHOP Study in the Treatment of Elderly Patients With Diffuse Large B-Cell Lymphoma: A Study by the Groupe d'Etude des Lymphomes de l'AdulteJournal of Clinical Oncology, 2005
- R-CHOP-14 in patients with diffuse large B-cell lymphoma: Feasibility and preliminary efficacyLeukemia & Lymphoma, 2005
- Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHLBlood, 2004