Study Shows Brostallicin in Combination with Cisplatin isWell-Tolerated and Produces Prolonged Disease Stabilization inPatients with Platinum-Resistant CancersPhase I Study Opens Path to Explore Brostallicin's Unique Mechanism of Killing Tumor Cells in Combination with Widely-Used Anti-Cancer Compound; Dose Established for Phase II Combination Studies
BARCELONA, Spain, September 27, 2007 /PRNewswire-FirstCall/ -- Systems Medicine, LLC (SM), a wholly-owned subsidiary of Cell Therapeutics, Inc. (CTI) , announced that preliminary data from a phase I dose-escalation study of brostallicin was presented at the 14th European Cancer Conference (ECCO 14) in Barcelona. In a presentation, data on brostallicin in combination with cisplatin (cDDP) showed the dose-limiting toxicities to be febrile neutropenia and fatigue. Prolonged disease stabilization was seen in patients with advanced solid tumors who had relapsed after prior treatment regimens. Of the 21 patients treated, 14 patients experienced disease stabilization with 7 patients experiencing disease stabilization for more than 18 weeks (18-31 weeks).
"This study was designed based on the unique pharmacology of brostallicin, which suggests that tumors that express high levels of GST, a common mechanism of resistance to platinum agents, would be very sensitive to this novel agent especially in combination with cDDP," said Steve Weitman, M.D., of Systems Medicine. "Despite having failed multiple prior treatment regimens, prolonged disease stabilization was achieved in a substantial number of patients studied. Further studies of brostallicin in combination with cisplatin are warranted."
The primary study objective was to determine the dose-limiting toxicities (DLT) of the combination regimen during the first cycle and the recommended dose for phase II studies. No patients experienced DLTs at the 5 or 7 mg/m2 dose, while two patients experienced DLTs at the 9 mg/m2 dose, including one patient with febrile neutropenia and one patient with fatigue lasting 19 days. The dose for phase II studies of brostallicin in combination with cDDP was defined as brostallicin 7 mg/m2 and cDDP 75 mg/m2 every three weeks in patients with solid tumors. The dose was determined to be safe and all toxicities (predominantly hematologic) were easily manageable and reversible.
About the Study
The phase I, multicenter, dose-escalation study of brostallicin in combination with cisplatin (cDDP) was conducted in patients with recurrent or metastatic solid tumors. Treatment cycles were three weeks. Brostallicin was escalated from 5 to 7 to 9 mg/m2 with a fixed dose of cDDP of 75 mg/m2.
Brostallicin, a novel synthetic second-generation DNA minor groove binder, has potent cancer killing activity and has demonstrated synergism in combination with standard cytotoxic agents as well as with newer targeted therapies in preclinical experimental tumors models. Brostallicin binds covalently to DNA within the DNA minor groove interfering with DNA division and leading to tumor cell death. More than 200 patients have been treated with brostallicin in single-agent and combination studies. Brostallicin had predictable and predominantly hematologic toxicities. Activity was demonstrated in a number of solid tumor types. A phase II study of brostallicin in relapsed/refractory soft tissue sarcoma met its pre-defined activity and safety hurdles and resulted in a first-line phase II study that is currently being conducted by the European Organization for Research and Treatment of Cancer (EORTC).
About Systems Medicine (SM)
In July 2007, CTI acquired Systems Medicine (SM), a privately-held oncology company, in a stock-for-stock merger. SM applies a systems biology approach to drug development, combining pharmacogenomics and bioinformatics with experienced preclinical, clinical, and regulatory expertise to find and exploit a specific cancer's 'context of vulnerability.' Specifically, SM defines the molecular and genetic alterations (context) that cause cancer cells to be particularly sensitive (vulnerable) to a drug or combination of drugs -- the 'context of vulnerability'.
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.
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 brostallicin include risks associated with preclinical and clinical developments in the biopharmaceutical industry in general and with brostallicin in particular including, without limitation, the potential failure of brostallicin to prove safe and effective for treatment of solid tumors, determinations by regulatory, patent and administrative governmental authorities, competitive factors, technological developments, costs of developing, producing and selling brostallicin, 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 Italian law, CTI is under no obligation to (and expressly disclaims any such obligation to) update or alter its forward-looking statements whether as a result of new information, future events, or otherwise.
Posted: September 2007