Cell Therapeutics, Inc. Release: Pivotal Trial To Evaluate Comparative Effectiveness Of XYOTAX(TM) To Taxol(R) In Women With Advanced Lung Cancer

SEATTLE, Dec. 6 /PRNewswire-FirstCall/ -- Cell Therapeutics Inc. (CTI) today announced plans to initiate a clinical trial in women of XYOTAX (paclitaxel poliglumex) versus paclitaxel chemotherapy for the treatment of PS2 (poor performance status) patients with chemotherapy-naive advanced stage non-small cell lung cancer (NSCLC). The trial, known as PIONEER 1, is the first approval trial for lung cancer exclusively targeting women and is expected to enroll 600 patients over the next 12 to 14 months.

"Gaining a better understanding of the biological role of estrogen in the development and progression of lung cancer has become increasingly important, especially with the growing number of women, including non-smokers, being diagnosed often at younger age than men and with different outcomes than men," said Kathy Albain, M.D., Professor of Medicine, Hematology/Oncology and Director, Thoracic Oncology and Breast Clinical Research, Loyola University Health System, and chair of the PIONEER 1 clinical trial steering committee. "Clinical trials that focus on and exploit new data on the biology of lung cancer in women are long overdue. Outcomes will be instrumental in developing tailored therapies, possibly based on gender but even more so, on the molecular biology of the disease. The exploratory data from the initial XYOTAX studies are provocative and validate the design of the PIONEER 1 prospective study."

Data presented at Chemotherapy Foundation Symposium XXIII

This news comes on the heels of a presentation at Chemotherapy Foundation Symposium XXIII in New York City early last month in which new data were presented that may support the scientific rationale of an enhanced survival benefit of women with NSCLC treated with XYOTAX versus standard chemotherapy.

In his presentation, Suresh Ramalingam, M.D., Assistant Professor of Medicine, University of Pittsburgh Cancer Institute noted that the estrogen receptor-mediated pathway plays an important role in NSCLC biology in both men and women. Presenting preliminary data, Ramalingam reported that exposure of lung cancer cells to estrogen increases the gene expression of cathepsin B, a critical enzyme that metabolizes XYOTAX, releasing active paclitaxel within the tumor cell.

"These data suggest that patients with normal estrogen levels may benefit due to the favorable effect of estrogen on XYOTAX metabolism," noted Dr. Ramalingam.

Mark A. Socinski, M.D., Associate Professor of Medicine, Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center at the University of North Carolina Chapel Hill, presented clinical data from a pooled analysis of CTI's STELLAR 3 and 4 trials. In the 198 women treated on those trials, superior survival was observed in those who received XYOTAX (p=0.03). The most notable impact was among women less than 55 years old and presumably pre-menopausal who were treated with XYOTAX compared to standard chemotherapy (median survival 10.0 vs. 5.3 months, hazard ratio=0.51, log rank p=0.038). While a survival trend (p=0.134) was observed in women 55 years of age and older (post-menopausal), the greater benefit observed among younger women is supportive of a positive impact of estrogen in XYOTAX patients. Further support for this was observed in the STELLAR 3 trial, where blood estrogen levels were retrospectively analyzed. Women with higher estrogen levels, regardless of age, who were treated with XYOTAX in combination with carboplatin had a significant improvement in overall survival compared to women treated with paclitaxel in combination with carboplatin (median survival 10.2 months vs. 5.5 months, hazard ratio=0.54, log rank p=0.039).

"These data are exciting and provide a strong scientific link between estrogen and the effectiveness of XYOTAX, a biologically-enhanced chemotherapy agent, in treating women with lung cancer," stated Dr. Socinski. "These findings open the door to a new avenue of clinical research for gender-specific therapy, not only in lung cancer but in a number of cancers that are known to express the estrogen receptor."

"These presentations highlight how an effect of estrogen on XYOTAX metabolism by tumors may lead to enhanced efficacy in women with lung cancer. It is important to note that XYOTAX was similar in efficacy to standard agents in men but has notable safety and convenience advantages over existing therapies in men and women, particularly when used as a single agent," noted Jack W. Singer, M.D., Chief Medical Officer at CTI.

Gender Differences in Lung Cancer

Several studies have indicated that compared to men, women who smoke are more likely to develop lung cancer at a younger age and at lower levels of exposure to cigarette smoke. Non-smoking women are at higher risk for developing lung cancer than non-smoking men. Research to date has focused on the influence of pharmacogenetic differences between men and women and on the role of estrogen to explain these findings. Estrogen enhances the effects of carcinogens in the environment and in smoke, possibly leading to a higher risk for NSCLC and once it occurs, appears to enhance its development.

Since women have higher levels of estrogen than men, and younger women have higher levels of estrogen than older women, this may in part be responsible for their higher risk for NSCLC. Developing therapies that are favorably influenced by estrogen may provide a gender-targeted therapeutic approach to the treatment of NSCLC.

PIONEER 1 Clinical Trial Protocol

The PIONEER 1 clinical trial is expected to begin patient recruitment in December 2005 in the United States, Eastern Europe, and Latin America with enrollment of 600 PS2 chemotherapy-naïve women with advanced stage NSCLC. Each study arm of approximately 300 patients will be randomized to receive either XYOTAX 175mg/m2 or paclitaxel 175mg/m2 once every three weeks. The primary endpoint is superior overall survival with several secondary endpoints including disease control, response rate in patients with measurable disease, time to disease progression, and disease-related symptoms.


XYOTAX (paclitaxel poliglumex) is a biologically-enhanced chemotherapeutic that links paclitaxel, the active ingredient in Taxol(R), to a biodegradable polyglutamate polymer, which results in a new chemical entity. When bound to the polymer, the chemotherapy is rendered inactive potentially sparing normal tissue's exposure to high levels of unbound, active chemotherapy and its associated toxicities. Blood vessels in tumor tissue, unlike blood vessels in normal tissue, are porous to molecules like polyglutamate. Once inside the tumor cell, enzymes metabolize the protein polymer, releasing the paclitaxel chemotherapy. Based on preclinical studies, it appears that XYOTAX is preferentially trapped in the tumor blood vessels allowing significantly more of the dose of chemotherapy to localize in the tumor. Preclinical and clinical studies support that XYOTAX metabolism by lung cancer cells may be influenced by estrogen which could lead to enhanced release of paclitaxel and efficacy in women with lung cancer over non-biologically enhanced chemotherapeutic agents.

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.cticseattle.com.

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 XYOTAX include risks associated with preclinical and clinical developments in the biopharmaceutical industry in general and with XYOTAX in particular including, without limitation, the potential failure of XYOTAX to prove safe and effective or be approved for use in non-small cell lung cancer, risks that the effect of estrogen seen in preclinical studies do not result in a gender effect or improvement in survival of women with non-small cell lung cancer, risks related to the initiation, accrual, and results of the PIONEER 1 trial, determinations by regulatory, patent and administrative governmental authorities, competitive factors, technological developments, costs of developing, producing and selling XYOTAX, 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. 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. Taxol(R) is a registered trademark of Bristol-Myers Squibb Co.

Cell Therapeutics, Inc.

CONTACT: Investors, Leah Grant, +1-206-282-7100, or fax, +1-206-272-4434,or invest@ctiseattle.com, or media, Susan Callahan, +1-206-272-4472, orfax, +1-206-272-4434, or media@ctiseattle.com, both of Cell Therapeutics,Inc.

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