Promising Preliminary Results on Radiation Sensitization from Phase II Trial May Serve as Additional Registration Direction for OPAXIO
ORLANDO, Fla., June 3 /PRNewswire-FirstCall/ -- Cell Therapeutics, Inc. (“CTI”) announced today that, in a study released from Brown University at the 2009 American Society for Clinical Oncology (ASCO) Annual Meeting, patients with cancer of the lower esophagus had evidence of a high pathological complete response (“CR”) rate when given OPAXIO, a biologically enhanced paclitaxel, in addition to cisplatin and full-course radiotherapy.
Concurrent chemotherapy with 50.5 Gy of radiation is the standard pre-surgical therapy for patients with potentially resectable, locally-advanced esophageal cancer. Although the addition of chemotherapy to radiation is beneficial, the cure rate for esophageal cancer is low. Standard neoadjuvant treatment for esophageal cancer uses a regimen of cisplatin, and fluorouracil (5-FU) chemotherapy with concurrent radiation, a regimen associated with a 15% to 17% pathologic CR rate (complete elimination of the cancer in the surgical specimen) and a high incidence of Grade 3-4 toxicity to the upper gastrointestinal track necessitating prophylactic insertion of feeding tubes. Published preclinical studies have demonstrated that, unlike standard paclitaxel and other chemotherapeutic agents that enhance radiation killing by a factor of 1.5 to 2.0, OPAXIO increases tumor specific radiation cell kill by a factor of 7.2 to 8.4 -fold (Milas Luka et al, Poly(L-glutamic acid)-paclitaxel conjugate is a potent enhancer of tumor radiocurability, Int’l J. Radiat. Oncol. Biol. Phys. 55(3), 707-12 (2003)).
The Brown University Oncology Group lead by Dr. Howard Safran published preliminary data on their phase II trial in the ASCO proceedings. In this study, which follows their earlier report of a phase IB trial (Dipetrillo,Thomas et al, Am. J. Clin. Oncol. 4:376-9 (2006)), patients with pathologically confirmed, locally advanced adenocarcinoma or squamous cell carcinoma of the esophagus or gastro-esophageal junction with no evidence of distant metastasis received weekly paclitaxel poliglumex (50mg/m2) and cisplatin 25mg/m2 for six weeks with concurrent 50.5Gy of radiation. Twenty-three eligible patients were enrolled at the time of abstract submission. Five of the first 11 patients (45%) who underwent resection had a pathologic complete response. A prophylactic feeding tube was not routinely used. Grade 3-4 toxicity in the first 15 patients included dehydration (n=5), loss of appetite (n=5), esophagitis/dysphagia (n=4), nausea (n=2) and weight loss (n=1). The authors concluded that these preliminary data suggest paclitaxel poliglumex may provide enhanced radiation sensitization as compared to standard therapy. Accrual is continuing on this study.
“We are very encouraged by these preliminary phase II results. Patients who have a pathologic CR in most historical studies have had a major survival advantage over those patients with lesser responses. These interesting preliminary findings in an ongoing study indicate that paclitaxel poliglumex may be a uniquely active and selective radiosensitizing therapeutic. Most importantly, patient tolerability appears improved over standard therapy with 5-FU and cisplatin due to the lower incidence of severe gastrointestinal toxicity. It is likely that this is due to the selective accumulation of paclitaxel poliglumex in tumor tissue with continual slow release of the active agent, paclitaxel,” noted Jack Singer, M.D., Chief Medical Officer at CTI.
CTI plans to explore with the U.S. Food and Drug Administration (the “FDA”) a potential U.S. phase III registration strategy for paclitaxel poliglumex in this indication given the high pathologic CR rates being reported in this study combined with the lower than expected gastrointestinal and other severe toxicities.
About OPAXIO(TM)
OPAXIO(TM) (paclitaxel poliglumex, CT-2103), which was formerly known as XYOTAX(TM), is an investigational, 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. Based on preclinical studies, it appears that OPAXIO is preferentially distributed to tumors due to their leaky blood vessels and trapped in the tumor bed allowing significantly more of the dose of chemotherapy to localize in the tumor than with standard paclitaxel. Once inside the tumor cell, enzymes metabolize the protein polymer, releasing the paclitaxel chemotherapy. Preclinical and clinical studies support that OPAXIO 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 compared to standard therapies.
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 OPAXIO include risks associated with preclinical and clinical developments in the biopharmaceutical industry in general, and with OPAXIO in particular, including, without limitation, the potential for OPAXIO to be proved safe and effective (or to achieve response rates) for the treatment of the indications noted in this press release or any other indication, determinations by regulatory, patent and administrative governmental authorities, the possibility that the FDA will not approve a phase III registration strategy for paclitaxel poliglumex if proposed by CTI, CTI’s ability to continue to raise capital as needed to fund its operations, competitive factors, technological developments, and costs of developing, producing and selling OPAXIO. You should also review the risk factors listed or described from time to time in CTI’s filings with the Securities and Exchange Commission including, without limitation, CTI’s most recent filings on Forms 10-K, 10-Q and 8-K. 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.
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