Researchers from France, Germany and Cell Therapeutics have reported that pixantrone produces a high response rate without a decrease in cardiac function in patients with non-Hodgkin’s lymphoma (NHL) previously treated with anthracyclines. This phase II study was reported at the 2004 meeting of the American Society of Hematology in San Diego December 4-7.

Anthracyclines are among the most active anti-cancer compounds, especially for the treatment of NHL and breast cancer. The main long-term toxicity of anthracyclines is cardiac toxicity, which can become manifest many years after treatment has been discontinued. There have been attempts to decrease cardiotoxicity by pegalation and liposomal encapsulation as in Doxil®. One mechanism thought to be responsible for the cardiac toxicity of anthracyclines is through the production of free-radicals. Pixantrone was designed by eliminating to OH molecules while retaining the rest of the mitoxantrone molecule. This agent was tested in a phase I trial presented at ASH 2003, leading to the current phase II trial.

This trial involved 21 patients with previously treated lymphoma who had received a median cumulative doxorubicin-equivalent dose of 327 mg/m2 (50-460). Patients were treated with up to 6 cycles of pixantrone. The overall response rate was 62%, with a complete response rate of 33%. Left ventricular ejection fraction performed in 14 patients after 3-4 cycles of therapy showed no change and the same test in 7 patients after 6 cycles of therapy also showed no change.

Comments: The development of a truly non-cardiotoxic anthracycline for first-line treatment would be a great advance. Further studies with a long follow-up will be required to determine if pixantrone is such a drug.

Reference: Herbrecht R, Borchmann P, Wilhelm M, et al. Preliminary phase II results of pixantrone (BBR) in combination with cyclophosphamide, vincristine and prednisone in patients with relapsed aggressive non-Hodgkin’s lymphoma. Proceedings of the American Society of Hematology. Blood. 2004;104:682a, abstract number 2489.