OPAXIO Produces High Rates of Pathologic Complete Remission in Patients with Advanced Esophageal Cancer; Study Paves Way for Pot
October 01 2009 - 1:30AM
PR Newswire (US)
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
http://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. 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®, 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
http://www.celltherapeutics.com/. Sign up for email alerts and get
RSS feeds at our Web site,
http://www.celltherapeutics.com/investors_news.htm 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. Media
Contact: Dan Eramian T: 206.272.4343 C: 206.854.1200 E:
http://www.celltherapeutics.com/press_room Investors Contact: Ed
Bell T: 206.282.7100 Lindsey Jesch Logan T: 206.272.4347 F:
206.272.4434 E: http://www.celltherapeutics.com/investors Medical
Information Contact: T: 800.715.0944 E: DATASOURCE: Cell
Therapeutics, Inc. CONTACT: Dan Eramian, +1-206-272-4343, cell,
+1-206-854-1200, , or investors, Ed Bell, +1-206-282-7100, or
Lindsey Jesch Logan, +1-206-272-4347, fax, +1-206-272-4434, , all
of Cell Therapeutics, Inc.; or Medical Information, 1-800-715-0944,
Web Site: http://www.celltherapeutics.com/
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