Long-term follow-up of R-CHOP with bevacizumab as initial therapy for mantle cell lymphoma: clinical and correlative results. Academic Article Article uri icon

Overview

MeSH

  • Adult
  • Aged
  • Anemia
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Cell Line, Tumor
  • Cyclophosphamide
  • Doxorubicin
  • Fatigue
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Prednisone
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-1
  • Ventricular Dysfunction, Left
  • Vincristine

MeSH Major

  • Antineoplastic Combined Chemotherapy Protocols
  • Lymphoma, Mantle-Cell

abstract

  • Emerging evidence indicates that MCL has increased angiogenesis within the tumor microenvironment. We initiated a phase II trial to determine if the addition of bevacizumab to the standard R-CHOP regimen could enhance antitumor effects in patients with previously untreated MCL. Eleven patients with previously untreated MCL received bevacizumab at 15 mg/kg on day 1, and standard CHOP-21 (CHOP given every 21 days per cycle) with rituximab (375 mg/m(2) per cycle) on day 3 of each cycle for a total of 6 cycles. Planned study end points included safety and efficacy assessment, and exploratory analysis of angiogenic profiles. The study was suspended in August of 2010 based on safety findings in DLBCL (diffuse large B-cell lymphoma) of increased cardiovascular events with the regimen. Beyond the standard R-CHOP safety profile, Grade 3 left ventricular dysfunction developed in 2 patients (18%), Grade 1/2 hypertension, proteinuria, and bleeding each developed in 1 patient (9%). The overall response rate was 82% with 36% complete response (CR)/complete response unconfirmed (CRu). The median progression-free survival (n = 11) was 18 months (95% confidence interval, 3-not reached), and 3-year overall survival rate was 82%. Correlative studies showed increased vascular endothelial growth factor receptor 1 expression in tumor cells at baseline, and elevated levels of plasma vascular endothelial growth factor (VEGF) throughout treatment. The addition of bevacizumab to the standard R-CHOP regimen did not appear to significantly improve efficacy beyond that observed from previous studies using R-CHOP alone. Therapeutic strategies that provide sustained inhibition on VEGF-related and VEGF-independent targets within the tumor microenvironment might further improve antiangiogenic effects and warrant further exploration in MCL. Copyright © 2014 Elsevier Inc. All rights reserved.

publication date

  • April 2014

has subject area

  • Adult
  • Aged
  • Anemia
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols
  • Bevacizumab
  • Cell Line, Tumor
  • Cyclophosphamide
  • Doxorubicin
  • Fatigue
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lymphoma, Mantle-Cell
  • Male
  • Middle Aged
  • Prednisone
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-1
  • Ventricular Dysfunction, Left
  • Vincristine

Research

keywords

  • Clinical Trial, Phase II
  • Journal Article
  • Multicenter Study

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.clml.2013.10.002

PubMed ID

  • 24373788

Additional Document Info

start page

  • 107

end page

  • 113

volume

  • 14

number

  • 2