Pixurvi (pixantrone)

by Ross Bonander

Pixurvi (pixantrone) is a anti-cancer drug administered by injection currently under development by Cell Therapeutics for the treatment of relapsed or refractory non-Hodgkin lymphoma in patients who have failed first and second line therapy. Although the FDA granted pixantrone Orphan Drug Designation and fast-track status, the agency rejected an application to bring the drug to market following the drug's disappointing and incomplete phase III clinical trial results as reported to the FDA's Office of Oncology Drug Products in 2010. The manufacturer is appealing that decision.

Drug profile

• Class: Antitumor aza-anthracenedione
• Treatment type: Chemotherapy
• US approval: Currently unapproved
• Synonyms: BBR 2778
• FDA Use-in-Pregnancy Rating: N/A

What it's effective for and why

Pixantrone has yet to be proven to be effective against its primary indication, that of relapsed or refractory non-Hodgkin lymphoma in patients who have failed first and second line therapy. However, it was developed to have similar anticancer properties as anthracyclines such as doxorubicin but without the cardiotoxicity so strongly associated with that class of chemotherapeutic drugs. To date pixantrone has failed to bear this out.

Side effects: Overview

Predominant side effects of pixantrone in clinical trials to date include neutropenia, anemia, leukopenia, thrombocytopenia, pyrexia, coughing, nausea, peripheral edema, and abdominal pain. However, keep in mind that the broader and more complete toxicity and side effect profile of pixantrone has not been explored or fully catalogued, and patients taking pixantrone in future clinical trials are encouraged to report any and all side effects to their doctor or clinical trial regulators immediately.

Sources

• Lymphoma Information Network: FDA Rejects Pixantrone
• LIN: The other 70 percent
• Cell Therapeutics: Pixantrone
• Cell Therapeutics: Pixantrone fact sheet (PDF)
• FDA ODAC Briefing Document: Pixantrone (PDF)

Significant studies relating to pixantrone

• Borchmann P et al. Phase-II study of the new aza-anthracenedione, BBR 2778, in patients with relapsed aggressive non-Hodgkin's lymphomas. Haematologica. 2003 Aug;88(8):888-94.
• Engert A et al. EXTEND PIX301: a phase III randomized trial of pixantrone versus other chemotherapeutic agents as third-line monotherapy in patients with relapsed, aggressive non-Hodgkin's lymphoma. Clin Lymphoma Myeloma. 2006 Sep;7(2):152-4.
• Lim ST et al. A phase I/II trial of pixantrone (BBR2778), methylprednisolone, cisplatin, and cytosine arabinoside (PSHAP) in relapsed/refractory aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2007 Feb;48(2):374-80.