Michael A Fridrik1, Ulrich Jaeger2, Andreas Petzer3, Wolfgang Willenbacher4, Felix Keil5, Alois Lang6, Johannes Andel7, Sonja Burgstaller8, Otto Krieger9, Willi Oberaigner10, Kurt Sihorsch11, Richard Greil12. 1. Department of Internal Medicine 3 - Hematology and Oncology, Kepler University Hospital, Johannes Kepler University, Linz, Austria. Electronic address: michael.fridrik@akh.linz.at. 2. Medical University Vienna, Department of Medicine I, Hematology and Hemostaseology, Austria. 3. Barmherzige Schwestern Hospital Linz, Department of Medical Oncology, Hematology and Gastroenterology, Austria. 4. University of Innsbruck, Internal Medicine V: Hematology-Oncology, Austria. 5. Hanusch Hospital Vienna, Department of Medicine III: Hematology Oncology, Austria. 6. LKH Feldkirch, Department of Internal Medicine, Austria. 7. LKH Steyr, Department of Internal Medicine II, Austria. 8. Klinikum Wels-Grieskirchen, Department of Internal Medicine IV, Austria. 9. Elisabethinen Hospital Linz, Department of Internal Medicine I, Austria. 10. TILAK, Clinical Epidemiology, Austria. 11. AKH Linz, Department of Internal Medicine I, Austria. 12. Paracelsus University Hospital, Salzburg, Department of Medicine III, Austria.
Abstract
BACKGROUND:Chemoimmunotherapy containing rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) is the standard treatment for diffuse large B-cell lymphoma (DLBCL). Doxorubicin may induce early and late cardiotoxicity. Non-pegylated liposomal (NPL) doxorubicin may reduce cardiotoxicity. PATIENTS AND METHODS: Patients with untreated CD20+ DLBCL were randomised to conventional R-CHOP chemoimmunotherapy or rituximab, cyclophosphamide, non-pegylated liposomal doxorubicin, vincristine and prednisolone (R-COMP) with doxorubicin substituted by NPL-doxorubicin. Left ventricular ejection fraction (LVEF) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels were measured before each treatment cycle and after the end of treatment. RESULTS: The mean LVEF of 178 and 158 measurements in the R-COMP and R-CHOP arms was 63.31% and 62.25%, respectively (P = 0.167). During treatment the LVEF measurements were below 50% in 10/218 (4.6%) in the R-COMP arm and 31/196 (15.8%) in the R-CHOP arm (P<0.001). Thirty-six of 40 (90%) patients in the R-COMP arm, but only 24/36 (66.7%) in the R-CHOP arm had all NT-proBNP levels below 400 pg/ml during and at the end of treatment (P = 0.013). There were more serious adverse events in the R-CHOP arm (26 versus 40, P = 0.029). Infections were more common (15 versus 28) in the R-CHOP arm. INTERPRETATION: In patients with normal cardiac function, six cycles of R-CHOP resulted in a low rate of early cardiotoxicity. NPL-doxorubicin did not reduce cardiotoxicity, although cardiac safety signals were elevated in R-CHOP compared to R-COMP. FUNDING: Cephalon provided the Arbeitsgemeinschaft Medikamentöse Tumortherapie with NPL-doxorubicin and an unrestricted grant, but was not involved in the study protocol, data acquisition, data analysis or the writing of the paper.
RCT Entities:
BACKGROUND: Chemoimmunotherapy containing rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) is the standard treatment for diffuse large B-cell lymphoma (DLBCL). Doxorubicin may induce early and late cardiotoxicity. Non-pegylated liposomal (NPL) doxorubicin may reduce cardiotoxicity. PATIENTS AND METHODS: Patients with untreated CD20+ DLBCL were randomised to conventional R-CHOP chemoimmunotherapy or rituximab, cyclophosphamide, non-pegylated liposomal doxorubicin, vincristine and prednisolone (R-COMP) with doxorubicin substituted by NPL-doxorubicin. Left ventricular ejection fraction (LVEF) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels were measured before each treatment cycle and after the end of treatment. RESULTS: The mean LVEF of 178 and 158 measurements in the R-COMP and R-CHOP arms was 63.31% and 62.25%, respectively (P = 0.167). During treatment the LVEF measurements were below 50% in 10/218 (4.6%) in the R-COMP arm and 31/196 (15.8%) in the R-CHOP arm (P<0.001). Thirty-six of 40 (90%) patients in the R-COMP arm, but only 24/36 (66.7%) in the R-CHOP arm had all NT-proBNP levels below 400 pg/ml during and at the end of treatment (P = 0.013). There were more serious adverse events in the R-CHOP arm (26 versus 40, P = 0.029). Infections were more common (15 versus 28) in the R-CHOP arm. INTERPRETATION: In patients with normal cardiac function, six cycles of R-CHOP resulted in a low rate of early cardiotoxicity. NPL-doxorubicin did not reduce cardiotoxicity, although cardiac safety signals were elevated in R-CHOP compared to R-COMP. FUNDING: Cephalon provided the Arbeitsgemeinschaft Medikamentöse Tumortherapie with NPL-doxorubicin and an unrestricted grant, but was not involved in the study protocol, data acquisition, data analysis or the writing of the paper.
Authors: Alden A Moccia; Kimberly Schaff; Ciara Freeman; Paul J Hoskins; Richard J Klasa; Kerry J Savage; Tamara N Shenkier; Randy D Gascoyne; Joseph M Connors; Laurie H Sehn Journal: Blood Adv Date: 2021-03-09
Authors: Katarzyna Mizia-Stec; Marek Elżbieciak; Maciej T Wybraniec; Monika Różewicz; Artur Bodys; Wojciech Braksator; Zbigniew Gąsior; Piotr Gościniak; Tomasz Hryniewiecki; Jarosław Kasprzak; Andrzej Wojtarowicz; Barbara Zdziarska; Edyta Płońska-Gościniak Journal: Med Oncol Date: 2017-12-22 Impact factor: 3.064