OPAXIO Produces High Rates of Pathologic Complete Remission in Patients with Advanced Esophageal Cancer; Study Paves Way for Potential Registration Trial as Radiation Sensitizer
Phase II results to be presented at Proffered Session of International Society of Gastrointestinal Oncology
PHILADELPHIA, Oct. 1 /PRNewswire-FirstCall/ -- Cell Therapeutics, Inc. ("CTI") (NASDAQ and MTA: CTIC) announced today that, in a study from Brown University to be presented by Howard Safran, M.D., head of the Brown University Oncology Group, in the proffered oral session at the Annual Meeting of the International Society of Gastrointestinal Oncology (ISGIO) in Philadelphia, Pennsylvania patients with cancer of the lower esophagus demonstrated a high rate of complete remission (CR) when given OPAXIO(TM) (paclitaxel poliglumex), a biologically enhanced paclitaxel, when administered in combination with standard cisplatin and concurrent radiation.
The phase II study, led by Dr. Safran, enrolled 40 patients with pathologically-confirmed, locally-advanced adenocarcinoma or squamous cell carcinoma of the esophagus or gastro-esophageal junction with no evidence of distant metastasis. The patients received weekly paclitaxel poliglumex (50mg/m2) and cisplatin 25mg/m2 for six weeks with concurrent 50.5Gy of radiation. Of the first 28 patients undergoing surgery, all with adenocarcinoma, eight of 28 (28.5%), have achieved a pathologic CR. No patients required a feeding tube, in contrast to historical studies using the standard regimen where the large majority of patients require a feeding tube. There were no grade 4 hematologic toxicities; grade 3 hematologic toxicity included neutropenia (n=2) and anemia (n=1). Four of 35 patients experienced grade 4 non-hematologic toxicities, which included electrolyte abnormalities, glucose intolerance, hypersensitivity reaction and thromboembolus. Eleven of 35 patients had grade 3 non-hematologic toxicities including electrolyte abnormalities (n=5), nausea (n=3), dysphagia (n=2), fatigue (n=2), glucose intolerance (n=2), and hypersensitivity reaction (n=1). Grade 3 anorexia was reported in only one patient who subsequently was given total parenteral nutrition. No patients developed neuropathy.
"These are very promising results, as standard platinum, 5-FU, and radiation-based regimens for this disease are accompanied by a high incidence of severe radiation esophagitis, requiring patients to receive nutrition through feeding tubes," said Dr. Safran. "Paclitaxel poliglumex's selective radiation enhancement preclinical profile is being validated by the high rates of pathologic complete remission and low rates of severe regional side effects we have observed in this phase 2 study. Our results justify proceeding to a randomized, controlled trial to definitively prove the impressive clinical benefit we have observed in our experience with this novel bioengineered paclitaxel agent," Dr. Safran added.
"We look forward to discussing with the Food and Drug Administration a potential phase III registration strategy for this indication," said Jack Singer, M.D., Chief Medical Officer at CTI. "This would be the first registration study for a radiation sensitizing agent in this indication."
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, which is a regimen associated with 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 presentation slides are available at www.celltherapeutics.com/investor_updates.
CTI has an existing license and co-development agreement with Novartis for OPAXIO, which also provides Novartis with an option to enter into an exclusive worldwide license to develop and commercialize pixantrone based upon agreed terms.
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 TaxolÂ®, 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.
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 and the trading price of CTI's securities. 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 potential that OPAXIO will not produce high rates of complete remission in patients with advanced esophageal cancer, the possibility that the registration trial for OPAXIO as a radiation sensitizer will not occur, the possibility that the U.S. Food and Drug Administration will not approve a phase III registration strategy for paclitaxel poliglumex if proposed by CTI, the potential that Novartis will not exercise its option, 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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Posted: October 2009