Comparison of pixantrone-based regimen (CPOP-R) with doxorubicin-based therapy (CHOP-R) for treatment of diffuse large B-cell lymphoma.
BACKGROUND
Pixantrone is an aza-anthracenedione with enhanced, preclinical antitumor activity and reduced cardiotoxicity compared with doxorubicin.


METHODS
We compared the efficacy and toxic effect of CPOP-R (substituting pixantrone for doxorubicin) against CHOP-R in untreated, diffuse large B-cell lymphoma (DLBCL) patients. The primary objective was to demonstrate non-inferiority of CPOP-R by complete response/complete response unconfirmed (CR/CRu) rate.


RESULTS
The CR/CRu rate for CPOP-R was 75% versus 84% for CHOP-R. Three-year overall survival was lower for CPOP-R (69% versus 85%) (P = 0.029). Median progression-free survival (PFS) was not reached for CPOP-R and was 40 months for CHOP-R [HR 95% confidence interval (CI) = 1.02 (0.60, 1.76), P = 0.934]. Fewer CPOP-R patients developed congestive heart failure (CHF) (0% versus 6%, P = 0.120), ≥ 20% declines in ejection fraction (2% versus 17%, P = 0.004), or elevations in troponin-T (P = 0.003).


CONCLUSIONS
CPOP-R is an active regimen with modestly lower response rates than CHOP-R but similar PFS and event-free survival. This study demonstrates a substantially lower cardiotoxicity of pixantrone compared with doxorubicin when used as first-line therapy in DLBCL.
Department of Oncology and Hematology, Hôpital de Hautepierre, Strasbourg, France. Electronic address: raoul.herbrecht@chru-strasbourg.fr.
R
R
Herbrecht
Cell Therapeutics, Inc., Seattle, USA.
P
P
Cernohous
Department of Internal Medicine 1, Klinikum der Universität zu Köln, Köln, Germany.
A
A
Engert
Hematology Service, Hôtel Dieu 1, Nantes, France.
S
S
Le Gouill
Division of Hematology, Queen Elizabeth II Health Sciences Centre, Halifax, Canada.
D
D
Macdonald
Cell Therapeutics, Inc., Seattle, USA.
C
C
Machida
Cell Therapeutics, Inc., Seattle, USA.
H
H
Myint
Department of Oncology/Hematology, Sharp HealthCare, San Diego, USA.
A
A
Saleh
Cell Therapeutics, Inc., Seattle, USA.
J
J
Singer
Oncology and Hematology, Klinikum Nürnberg Nord Medizinische Klinik 5, Nürnberg, Germany.
M
M
Wilhelm
Clinical Haematology, Ottawa Hospital, Ottawa, Canada.
R
R
van der Jagt
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000139:chemically induced*; D006801:Humans; D007546:Isoquinolines / Q000009:adverse effects* / Q000627:therapeutic use*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D000069283:Rituximab; D013318:Stroke Volume / Q000187:drug effects; D013534:Survival; D015996:Survival Rate; D059005:Topoisomerase II Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D020107:Troponin T / Q000378:metabolism; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
D000903:Antibiotics, Antineoplastic; D058846:Antibodies, Monoclonal, Murine-Derived; D007546:Isoquinolines; D059005:Topoisomerase II Inhibitors; D020107:Troponin T; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; C086548:pixantrone; D011241:Prednisone
CPOP-R; diffuse large B-cell lymphoma; doxorubicin; pixantrone; randomized clinical trial