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Publication on Pixantrone Preclinical Studies Demonstrates Reduced,Cardiotoxicity Compared to Equiactive Doses of Doxorubicin and,Mitoxantrone

nti-cancer drugs following disease relapse. Pixantrone, a novel anthracenedione analog, was developed to reduce treatment-related cardiotoxicity while retaining efficacy.

These findings suggest that pixantrone may have potential use in patients heavily pre-treated with anthracyclines, in patients with cardiac disorders, and in patients who might benefit from longer-term anthracycline therapy than can be administered with currently approved agents.

Details of the Preclinical Studies

The studies were designed to evaluate the potential cardiotoxicity of pixantrone in mice pre-treated with doxorubicin and to evaluate the potential cardiotoxicity of pixantrone as a single agent compared to doxorubicin and mitoxantrone. Mice pre-treated with a cardiotoxic dose of doxorubicin were then administered a saline placebo control, doxorubicin, pixantrone, or mitoxantrone. Mice that received a second cycle of doxorubicin or mitoxantrone developed marked or severe cardiotoxicity. Mice that received the placebo or pixantrone as the second cycle had slightly increased mean total cardiotoxicity score, indicating that earlier exposure to doxorubicin may continue to damage the heart. While cardiotoxicity observed in the mice treated with pixantrone was not statistically different compared to mice treated with placebo, it was statistically different from that observed in the groups treated with doxorubicin or mitoxantrone. In the mice pre-treated with doxorubicin, a second cycle of mitoxantrone or pixantrone resulted in mortality of 33 percent and 27 percent, respectively.

Mice that received two consecutive cycles of pixantrone as a single agent showed no significant cardiotoxicity and had a mean total toxicity score that was statistically similar to the placebo. The severity and extent of observed damage to heart tissue was minimal and considered reversible. However, mice receiving two cycles of doxorubicin or mitoxantrone experienced marked cardiac damage th
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