Open Access Open Badges Study protocol

Significant dose Escalation of Idarubicin in the treatment of aggressive Non- Hodgkin Lymphoma leads to increased hematotoxicity without improvement in efficacy in comparison to standard CHOEP-14: 9-year follow up results of the CIVEP trial of the DSHNHL

Karin Hohloch1, Carsten Zwick2, Marita Ziepert3, Dirk Hasenclever3, Ulrich Kaiser4, Andreas Engert5, Heinz-Gert Höffkes6, Frank Kroschinsky7, Rolf Mesters8, Andreas C Feller9, Markus Löffler3, Lorenz Trümper1*, Michael Pfreundschuh2 and On behalf of the the German High-Grade Non-Hodgkin´s Lymphoma Study Group (DSHNHL)

Author Affiliations

1 Department of Hematology and Oncology, Georg August University, 37099 Göttingen, Germany

2 Department Internal Medicine I, University of Saarland, 66421 Homburg/Saar, Germany

3 Institue for Medical Informatics, Statistics and Epidemiology, University of Leipzig, 04107 Leipzig, Germany

4 Department of Hematology, St Bernward Hospital, 31134 Hildesheim, Germany

5 Department of Internal Medicine I, University of Köln, 50937 Köln, Germany

6 Department of Hematology, City Hospital Fulda, 36043 Fulda, Germany

7 Department of Hematology and Oncology, University Hospital, 01307 Dresden, Germany

8 Department of Hematology and Oncology, University Hospital, 48149 Münster, Germany

9 Institute of Pathology, Medical University of Lübeck, 23538 Lübeck, Germany

For all author emails, please log on.

SpringerPlus 2014, 3:5  doi:10.1186/2193-1801-3-5

Published: 3 January 2014



Dose escalation and modification of CHOP has improved the prognosis of patients with aggressive lymphoma; even in the rituximab era, dose escalation for high-risk patients is exploited and frequently limited by drug toxicity. Idarubicin (Id) is a 4-demethoxy anthracycline analogue of daunorubicin with activity against lymphoma and has been reported to cause less cardiotoxicity than other anthracylines. The aim of this study was to replace doxorubicine with idarubicin in the CHOEP regimen and to find the maximum tolerable dose (MTD) of idarubicin based on hematotoxicity.

Patients and methods

Between 11/96 and 09/98, 64 patients (pts) aged 18–75 yrs (pts. 18–60, LDH not elevated, >60 years all risk groups) with newly diagnosed aggressive lymphoma received 6 cycles of CIVEP-14 with an escalating dose of idarubicin, consisting of idarubicin (11–16 mg/m2 d1) and standard doses of cyclophosphamide, vincristine, etoposide, and prednisone with G-CSF support.


55 pts (median age 56 yrs) were evaluable for a final analysis with a median observation time of 9.3 years. The CR-rate was 77.4% ; the 5 and 8-year-EFS rates were 46.4% (95%CI 32.5-60.3%) and 43.5% (29.4-57.6%), respectively, and the 5- and 8 yr OS rates were 64.6% (51.7-77.5%) and 59.9% (46.4-73.4%). 14/55 patients have died due to lymphoma progression, and 2/55 patients (3.6%) due to treatment related toxicity, 4/55 due to other causes (3 infections, 1 acute heart failure). In a matched pair analysis comparing CHOEP-14 and CIVEP-14, CIVEP-14 had a higher hematotoxicity with no significant differences in the event free and overall survival for the two regimens.


Thus, idarubicin cannot be used instead doxorubicin even if its dose is escalated to achieve similar hematotoxicity. Doxorubicin remains the standard anthracycline for the treatment of aggressive NHL.

Aggressive B-cell lymphoma; Anthracycline; Dose escalation; Toxicity