Cell Therapeutics, Inc. (CTI) announced the publication of results posted in the online journal of Cancer of a phase I-II study that evaluated the safety and efficacy of pixantrone when used in combination with Fludarabine, Dexamethasone and Rituximab (FPD-R) replacing mitoxantrone in the standard FND-R regimen with FPD-R among 28 patients with relapsed or refractory Indolent Non-Hodgkin's Lymphoma (INHL).

The phase I-II study results showed that the FPD-R regimen was highly active in patients with relapsed or refractory INHL and produced Complete Responses (CR) in 63% of patients with an Overall Response Rate (ORR) of 89%. Responses were long lasting for a median of 23 months with the longest responding patient in remission longer than 40 months, with an estimated 92% survival rate at three years. The primary side effects were haematologic with 89% of patients developing grade 3-4 neutropenia, which was managed with growth factor administration. No patient developed congestive heart failure with no grade 3-4 cardiac side effects observed. The authors concluded the FPD-R regimen was well-tolerated and highly active in patients with relapsed or refractory INHL.

“This study further adds to the evidence of substantial anti-tumour activity for pixantrone in late stage lymphoid malignancies,” said Jack W Singer, MD, chief medical officer at CTI. “Of interest, of the 14 patients who were treated at MD Anderson Cancer Centre, six who obtained a complete remission and did not have a stem-cell transplant remain in complete remission 55 to 83 months after completing therapy. Seven went on to receive a stem-cell transplant and six remain in remission. The high and durable complete response rate in this study indicates that additional clinical trials in relapsed or refractory INHL are warranted.”

Pixantrone is a novel aza-anthracenedione that has distinct structural and physio-chemical properties that make its anti-tumour activity unique in this class of agents. Similar to anthracyclines, pixantrone inhibits Topo-isomerase II but unlike anthracyclines -- rather than intercalation with DNA -- pixantrone alkylates DNA -- forming stable DNA adducts with particular specificity for CpG-rich, hyper-methylated sites. These structural differences resulted in significantly enhanced anti-lymphoma activity compared to doxorubicin in preclinical models.

In addition, the structural motifs on anthracycline-like agents that are responsible for the generation of oxygen free radicals and the formation of toxic drug-metal complexes have also been modified in pixantrone in an effort to prevent the binding of iron and perpetuation of superoxide production -- both of which are the putative mechanism for anthracycline induced acute cardiotoxicity. These novel pharmacologic differences may allow re-introduction of anthracycline-like potency in the treatment of relapsed/refractory diffuse large lymphoma without unacceptable rates of cardiotoxicity.

CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable.