Pixantrone (BBR 2778) has reduced cardiotoxic potential in mice pretreated with doxorubicin: Comparative studies against doxorubicin and mitoxantrone

  title={Pixantrone (BBR 2778) has reduced cardiotoxic potential in mice pretreated with doxorubicin: Comparative studies against doxorubicin and mitoxantrone},
  author={Ennio Cavalletti and Luca Crippa and Patrizia Mainardi and Norberto Oggioni and Rosanna Cavagnoli and Ornella Bellini and Franca Sala},
  journal={Investigational New Drugs},
SummaryAnthracyclines and anthracenediones are important oncotherapeutics; however, their use is associated with irreversible and cumulative cardiotoxicity. A novel aza-anthracenedione, pixantrone (BBR 2778), was developed to reduce treatment-related cardiotoxicity while retaining efficacy. This study evaluates the cumulative cardiotoxic potential of pixantrone compared with equiactive doses of doxorubicin and mitoxantrone in both doxorubicin-pretreated and doxorubicin-naïve mice. CD1 female… 

Pixantrone: a novel aza-anthracenedione in the treatment of non-Hodgkin's lymphomas

When intensively pretreated patients with relapsed aggressive non-Hodgkin's lymphoma were treated with a cyclophosphamide, pixantrone, vincristine and prednisolone regimen (pixantrones substituted for doxorubicin in standard regimen), the overall response was 74% and complete response 57%.

Rethinking Drugs from Chemistry to Therapeutic Opportunities: Pixantrone beyond Anthracyclines.

Understanding the differences between pixantrone and anthracyclines or mitoxantrone may help one to appreciate how it worked in the phase 3 study that led to its approval in Europe and how it might work in many more patients in everyday clinical practice, were it properly perceived as a drug with its own characteristics and therapeutic potential.

Pixantrone, a new anticancer drug with the same old cardiac problems? An in vitro study with differentiated and non-differentiated H9c2 cells

This was the first in vitro study performed with PIX in H9c2 cells and it discloses worrying cytotoxicity at clinically relevant concentrations, although PIX toxicity was slightly higher in differentiated H9C2 cells.

The Novel Anthracenedione, Pixantrone, Lacks Redox Activity and Inhibits Doxorubicinol Formation in Human Myocardium: Insight to Explain the Cardiac Safety of Pixantrone in Doxorubicin-Treated Patients

Redox inactivity in the face of high cardiac uptake suggests that pixantrone might also be safe in doxorubicin-naïve patients, and correlates with the cardiac safety of pixanrone in doXorubICin-pretreated patients.

Randomized Phase II Study of Two Doses of Pixantrone in Patients with Metastatic Breast Cancer (NCCTG N1031, Alliance)

Pixantrone has insufficient activity in the second- and third-line MBC setting, however, it appears to have limited cardiotoxicity.

Pixantrone (BBR2778) Reduces the Severity of Experimental Autoimmune Myasthenia Gravis in Lewis Rats1

The effectiveness and the reduced cardiotoxicity make PIX a promising immunosuppressant agent suitable for clinical investigation in MG, although additional experiments are needed to confirm its safety profile in prolonged treatments.

Phase I/II study of pixantrone in combination with cyclophosphamide, vincristine, and prednisone in patients with relapsed aggressive non-Hodgkin lymphoma

Pixantrone is a potentially more effective, less cardiotoxic alternative to doxorubicin for patients with aggressive non-Hodgkin lymphoma (aNHL), in patients with relapsed aNHL who had previously received CHOP ± rituximab.

Inflammation as a Possible Trigger for Mitoxantrone-Induced Cardiotoxicity: An In Vivo Study in Adult and Infant Mice

Clinically relevant doses of MTX caused dissimilar responses in adult and infant mice, being that inflammation may be an important trigger to MTX-induced cardiotoxicity.



Preliminary Phase II Study Results of BBR2778 in Combination with Cyclophosphamide, Vincristine, and Prednisone in Patients with Relapsed Aggressive Non-Hodgkin’s Lymphoma.

These early results of the CPOP regimen with 150 mg/m² of pixantrone indicates a high response rate in pts with relapsed aggressive B cell lymphoma with an acceptable and manageable safety profile.

Bbr 2778, an Aza-anthracenedione Endowed with Preclinical Anticancer Activity and Lack of Delayed Cardiotoxicity

Although against in vivo models BBR 2778 was less potent than mitoxantrone and doxorubicin, its antitumor activity was equal or superior (in certain tumor models) to that of the above standard compounds.

A clinicopathologic analysis of adriamycin cardiotoxicity

It is suggested that the total dose of adriamycin should be limited to less than 550 mg/m2 to permit safer use of this efficacious cancer chemotherapeutic agent.

Early cardiotoxicity of the CHOP regimen in aggressive non-Hodgkin's lymphoma.

  • S. LimatK. Demesmay J. Cahn
  • Medicine
    Annals of oncology : official journal of the European Society for Medical Oncology
  • 2003
Early clinical and subclinical cardiotoxicity was frequent in patients receiving the CHOP regimen and Elderly patients appeared to be at higher risk.

Absence of delayed lethality in mice treated with aclacinomycin A

Two compounds that bind to or intercalate with DNA, e.g., adriamycin and ‘dihydroxyanthracenedione’, consistently caused delayed lethality if administered intraperitoneally (IP) and m-AMSA, which has neither the quinone function nor the para-hydroxyl groups, did not cause delayed deaths after IP administration.

Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients.

BACKGROUND With increasing doses the highly tumoricidal anthracycline drugs cause heart damage. Based on empirical drug limitations about 10-15% of patients will develop congestive heart failure

Cardiac toxicity 4 to 20 years after completing anthracycline therapy.

The 23% incidence of late cardiac abnormalities warrants continued evaluation of patients after anthracyclines to guide patient care and the design of future chemotherapeutic protocols.

Quantitative experimental evaluation of adriamycin cardiotoxicity in the mouse.

Adriamycin cardiotoxicity was morphologically evaluated in mice treated iv ten times at three dose levels which were equal to fixed fractions of the LD50 and good correlation between the degenerative heart lesions was found and allowed calculation of a median cumulative cardiotoxic dose.

Congestive heart failure in patients treated with doxorubicin

Doxorubicin is a highly effective and widely used cytotoxic agent with application that is limited by cardiotoxicity related to the cumulative dose of the drug, which is reflected in the incidence in the broader clinical oncology setting.