title: Incidence and risk-factors of CHOP/R-CHOP-related cardiotoxicity in patients with aggressive non-Hodgkin's lymphoma.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy, Besançon University Hospital, Besançon, France; Inserm UMR 1098, University of Franche-Comté, Besançon, France.
authors.forename: S
authors.initials: S
authors.lastname: Limat
authors.forename: E
authors.initials: E
authors.lastname: Daguindau
authors.forename: J-Y
authors.initials: JY
authors.lastname: Cahn
authors.forename: V
authors.initials: V
authors.lastname: Nerich
authors.forename: A
authors.initials: A
authors.lastname: Brion
authors.forename: S
authors.initials: S
authors.lastname: Perrin
authors.forename: M-C
authors.initials: MC
authors.lastname: Woronoff-Lemsi
authors.forename: E
authors.initials: E
authors.lastname: Deconinck
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D064730:Dexrazoxane / Q000627:therapeutic use*; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000139:chemically induced* / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D000069283:Rituximab; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D002316:Cardiotonic Agents; C571759:R-CHOP protocol; D064730:Dexrazoxane; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: anthracyclines; cardiotoxicity; dexrazoxane; lymphoma