Pixantrone Associated With Up to 4-Fold Reduction in Severe (Grade 3-4) Cardiac Toxicity When Compared to Doxorubicin in CHOP-R Regimen

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• USA - English

SEATTLE, May 18 /PRNewswire-FirstCall/ -- Cell Therapeutics, Inc. (CTI) (Nasdaq: CTIC; MTA) reported today preliminary cardiac safety results from a North American randomized phase II trial which substituted pixantrone for doxorubicin in the standard CHOP-R regimen. Called PIX203, the randomized trial compared CPOP-R directly to CHOP-R in the 1st line treatment of high risk patients with diffuse large B cell non-Hodgkin's lymphoma (DLBCL, NHL). While CHOP-R is considered the standard of care in front line treatment of DLBCL, exposure to cumulative doses of doxorubicin, an anthracycline, is associated with increasing incidence of irreversible, severe, and symptomatic cardiac toxicity. This correlation of doxorubicin exposure and increasing incidence of heart damage limits the use of doxorubicin beyond first line therapy and among patients with pre-existing cardiac disorders. Pixantrone  a novel aza-anthracenedione, unlike anthracycline drugs like doxorubicin, is a potent DNA alkylator which lacks the structural motifs of doxorubicin that are responsible for the formation of toxic drug metal complexes and oxygen free radical generation, the putative mechanisms for anthracycline-related cardiac toxicity.

Preliminary data from a safety analysis of PIX203 indicates that patients treated with the CPOP-R regimen experienced significantly less frequent major reductions (>=20%) in cardiac function as determined by serial measurements of left ventricular ejection fraction (LVEF) (2% vs. 13%, pixantrone vs. doxorubicin), less symptomatic congestive heart failure (CHF) (0% Vs 5%), and less severe grade 3-4 decline in LVEF (2% vs. 10%, pixantrone vs. doxorubicin respectively). Grade 3-4 treatment emergent adverse events including neutropenia, febrile neutropenia, and infection were similar between the arms. Preliminary investigator-determined response rates were also comparable (89% vs. 92%) between the two regimens.  Independent radiologic assessment of response and disease progression data is in progress and expected to be presented at national hematology society meetings later this year.

"These preliminary data from a randomized clinical trial appear to corroborate the preclinical and ex-vivo data regarding the differences in cardiotoxicity potential between doxorubicin and pixantrone," noted Jack Singer, M.D., Chief Medical Officer of CTI. "These data are consistent with the relatively low incidence of cardiac toxicity reported in the PIX301 randomized trial. In PIX 301, unlike PIX 203, patients had received near-lifetime limits of anthracyclines before entering the study, placing them at risk for unacceptably high incidence of severe cardiac toxicity if treated with additional doxorubicin. These data support the potential for pixantrone to be studied as first-line treatment for 20% of newly-diagnosed patients with pre-existing cardiac disease who are poor candidates for potentially curative treatment with doxorubicin-based regimens," Dr. Singer added.

CTI intends to file a marketing authorization application in Europe for pixantrone in the second half of 2010 and these results will be used as supportive data.

About RAPID (PIX203)

The RAPID trial is a first-line randomized phase II study of the CHOP-R versus CPOP-R in previously untreated aggressive NHL patients. The study is evaluating replacing doxorubicin in the standard CHOP-R combination regimen (cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab) with pixantrone to part of the CPOP-R regimen (cyclophosphamide, pixantrone, vincristine, prednisone and rituximab). The objective of the study is to demonstrate non-inferior complete response rates as the standard doxorubicin-based therapy with significantly less severe cardiac toxicities and other doxorubicinrelated toxicities on the CPOP-R arm of the study. 124 patients were enrolled in this study, 62 per arm.

About Cell Therapeutics, Inc.

Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable. For additional information, please visit www.CellTherapeutics.com.

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This press release includes forward-looking statements that involve a number of risks and uncertainties, the outcome of which could materially and/or adversely affect actual future results. Specifically, the risks and uncertainties that could affect the development of pixantrone include risks associated with preclinical and clinical developments in the biopharmaceutical industry in general and with pixantrone in particular including, without limitation, the potential failure of pixantrone to prove safe and effective for treatment of diffuse large B cell non-Hodgkin's lymphoma, determinations by regulatory, patent and administrative governmental authorities, competitive factors, technological developments, costs of developing, producing and selling pixantrone, and the risk factors listed or described from time to time in the Company's filings with the Securities and Exchange Commission including, without limitation, the Company's most recent filings on Forms 10-K, 8-K, and 10-Q. Except as may be required by law, CTI does not intend to update or alter its forward-looking statements whether as a result of new information, future events, or otherwise.

SOURCE Cell Therapeutics, Inc.