Incidence and risk-factors of CHOP/R-CHOP-related cardiotoxicity in patients with aggressive non-Hodgkin's lymphoma

J Clin Pharm Ther. 2014 Apr;39(2):168-74. doi: 10.1111/jcpt.12124. Epub 2014 Jan 3.

Abstract

What is known and objective: The CHOP regimen with rituximab (R-CHOP) remains the standard for chemotherapy in patients with aggressive non-Hodgkin's lymphoma (NHL). The cardiotoxicity of doxorubicin appears to be a key problem in clinical practice. We studied the cardiotoxicity of CHOP/R-CHOP regimen in a retrospective series. The prognostic factors of congestive heart failure (CHF) were investigated, including the impact of empirical cardioprotection by dexrazoxane.

Methods: Patients with an aggressive NHL between 1994 and 2005 were included. Cardiac events were defined as either a decline in resting left ventricular ejection fraction (LVEF) <50%, a decline in LVEF of ≥20% from baseline or as clinical evidence of CHF. The risk of cardiotoxicity was explored by the Kaplan-Meier method.

Results: The study included 180 consecutive patients. During the second period of the survey, cardioprotective therapy by dexrazoxane was administered to 45% of patients. The 5-year cumulative risks of cardiac events (29% vs. 8%) and clinical CHF (17% vs. 1·5%) varied significantly between the two periods of study (1994-2000 vs. 2001-2005). In multivariate analysis, use of dexrazoxane (HR = 0·1 [0·01-0·75], P = 0·02) and age < 60 years (HR = 0·4 [0·17-0·9], P = 0·03) appeared as protective factors of cardiac events.

What is new and conclusion: Our study confirmed the weight of cardiac toxic effect of CHOP ± R regimen. Even if the use of dexrazoxane is highly debatable in curative situations, it may be an effective prevention of cardiotoxicity in aggressive NHL patients.

Keywords: anthracyclines; cardiotoxicity; dexrazoxane; lymphoma.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived / adverse effects
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cardiotonic Agents / therapeutic use
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use
  • Dexrazoxane / therapeutic use*
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use
  • Female
  • Heart Failure / chemically induced*
  • Heart Failure / epidemiology
  • Heart Failure / prevention & control
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prednisone / adverse effects
  • Prednisone / therapeutic use
  • Retrospective Studies
  • Risk Factors
  • Rituximab
  • Vincristine / adverse effects
  • Vincristine / therapeutic use
  • Young Adult

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Cardiotonic Agents
  • R-CHOP protocol
  • Dexrazoxane
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • CHOP protocol