Paclitaxel Poliglumex (OPAXIO(TM)) Added to Cisplatin and Radiation Produces 45% Pathologic Complete Remissions in Patients With
June 03 2009 - 1:30AM
PR Newswire (US)
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") (Nasdaq and MTA: CTIC) 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
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. 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. 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 T: 206.272.4347 F: 206.272.4434
E: http://www.celltherapeutics.com/investors DATASOURCE: Cell
Therapeutics, Inc. CONTACT: Media, Dan Eramian, +1-206-272-4343,
cell, +1-206-854-1200, , or Investors, Ed Bell, +1-206-282-7100, or
Lindsey Jesch, +1-206-272-4347, fax, +1-206-272-4434, , all of Cell
Therapeutics, Inc. Web Site: http://www.celltherapeutics.com/
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