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Preclinical Study Provides Potential Mechanisms For Lower Cardiotoxicity In Patients With Multiply Relapsed Or Refractory Aggressive B-cell NHL Treated With PixuvriTM Who Received Prior Doxorubicin Therapy
Dec. 17, 2012 /PRNewswire/ -- Cell Therapeutics, Inc. (CTI) (Nasdaq and MTA: CTIC) today announced the publication of results from a preclinical study of Pixuvri
TM (pixantrone) in the
The Journal of Pharmacology and Experimental Therapeutics providing potential mechanisms for lower cardiotoxicity in patients treated with Pixuvri who received prior doxorubicin therapy. While CHOP-R is considered an effective therapy and is the standard of care in first line treatment of aggressive B-cell non-Hodgkin lymphoma (NHL), exposure to cumulative doses of doxorubicin, an anthracycline contained in this regimen, is associated with increasing the incidence of irreversible, severe, and symptomatic cardiac toxicity. The association with heart damage limits the use of doxorubicin and other anthracyclines beyond first line therapy and in patients with pre-existing cardiac disease.
Pixuvri is a novel anthracenedione that lacks the structural motifs that lead to the formation of reactive oxygen species or long-lived hydroxyl metabolites which are believed to be involved in cardiac damage. Although anthracycline induced cardiotoxicity is complex and multi-factorial, this study provides potential mechanisms by which Pixuvri avoids inducing this serious side effect. The study by
Giorgio Minotti, M.D., at the Center for Integrated Research and Drug Sciences, University Campus Bio-Medico,
Rome Italy, showed that in a human cardiac tissue model, both untreated and pretreated with doxorubicin, Pixuvri did not form reactive oxygen species or long lived hydroxymetabolites. In doxorubicin pretreated cardiac samples, Pixuvri also inhibited formation of the long-lived hydroxymetabolite of doxorubicin. These results suggest mechanisms for the low incidence of cardiotoxicity seen in clinical trials of Pixuvri in doxorubicin naive or pretreated patients.
"Anthracyclines are an effective therapy in aggressive B-cell NHL patients but their use is limited due to the association with cardiac damage," said Professor Minotti. "Cardiotoxicity complicates the clinical management of patients who relapse after first-line therapy as second or third line non-anthracycline chemotherapeutics might precipitate cardiotoxicity through multiple mechanisms. These data provide a biological rationale for the safety profile of Pixuvri and supports Pixuvri's role in treating multiply relapsed or refractory aggressive B-cell NHL."