Patients who had rapid disease progression on capecitabine
treatment(1) (N=9) and crossed over to take
eniluracil/5-FU/leucovorin (EFL) experienced the following:
-- 89% had clinical benefit(2)
-- 33% had tumor responses(3)
-- Ongoing median progression-free survival of 117 days vs. 42 days while
taking capecitabine
Adherex Technologies Inc. (TSX:AHX)(OTCQB:ADHXF) today announced
preliminary interim results from the ongoing Phase 2 clinical study
evaluating EFL in metastatic breast cancer patients. The results
were presented in a poster at the 2012 CTRC-AACR San Antonio Breast
Cancer Symposium, San Antonio, Texas, by Edgardo Rivera, MD,
Medical Director, Banner MD Anderson Cancer Center, Gilbert,
Arizona. The poster can be found on the www.adherex.com website
under the Investors and Media section.
"EFL could potentially allow patients who rapidly fail
capecitabine to continue with another oral 5-FU therapy rather than
switching to the less well-tolerated intravenous
microtubule-interfering agents," said Edgardo Rivera, MD. "We are
hopeful that a small clinical trial in patients with metastatic
breast cancer who failed capecitabine may be an attractive path to
rapidly demonstrate the clinical usefulness of EFL."
EFL was also well tolerated and active in the main study that
compares safety and anti-tumor activity of EFL (Arm 1) vs.
capecitabine (Arm 2) in metastatic breast cancer patients who had
been previously treated with an anthracycline and taxane. Arm 2
patients who have disease progression on capecitabine may crossover
to take EFL in Arm X. All study drugs are taken orally.
The EFL regimen was optimized according to the methods covered
in Adherex patent filings and are presented on the Adherex
website.
As of Oct. 29, 2012, 122 patients had tumor assessments.
Approximately 20% of patients were treated as 1st-line for
metastatic disease (80% as 2nd-line) and 70% had previous 5-FU
treatment(s). The preliminary interim results were based upon 68
patients in Arm 1, 54 patients in Arm 2 and 18 patients on Arm X.
Clinical benefit was 76%, 74% & 61%, and tumor response rate
was 25%, 26%, & 17% in Arms 1, 2, & X, respectively. One CR
occurred in Arm 1. For patients in Arm X who had rapidly failed
capecitabine, 89% had clinical benefit and 33% had tumor
responses.
The final efficacy and safety data from the study, including
progression-free survival (PFS), are expected to be released during
the second quarter of 2013.
Rosty Raykov, Chief Executive Officer of Adherex, said, "Thanks
to the scientific leadership of Dr. Tom Spector, we are pleased to
see these avenues opening up to potentially provide benefit to
cancer patients. Adherex is focused on finishing enrollment of the
study by the end of this year. The Company does not intend to raise
capital until final data is available from the study and partnering
opportunities are fully explored."
(1)Patients who rapidly failed capecitabine treatment had
disease progression (PD) within 70 days (one scan). (2)Clinical
benefit = (significant (partial, PR) + complete (CR) tumor
reduction + stable disease (SD)).(3)Tumor response = PR or CR.
About Eniluracil
Eniluracil is a mechanism-based inactivator of DPD, the enzyme
that rapidly breaks down 5-FU. Accordingly, Eniluracil increases
the 5-FU elimination half-life from about 15 minutes to 5 hours and
enables 5-FU to be administered orally, making it 100% orally
bioavailable. In addition, Eniluracil prevents the formation of
alpha-fluoro-beta-alanine (F-Bal), the 5-FU-breakdown product.
F-Bal appears to cause hand-foot syndrome and neurotoxicity. It
also decreases the antitumor activity of 5-FU in laboratory
animals. Furthermore, because DPD is present in variable levels,
the highly variable and nonlinear pharmacokinetics of 5-FU become
predictable and linear when DPD is inactivated by Eniluracil in
cancer patients.
The weekly regimen used in the current Phase 2 trial is based on
a Phase 1 Eniluracil/5-FU/Leucovorin trial that produced durable
tumor responses and no hand-foot syndrome in advanced colorectal
cancer patients who were refractory to intravenous 5-FU/Leucovorin.
In a similar Phase 2 study with capecitabine, no tumor responses
occurred and 87% of the patients experienced hand-foot syndrome, a
painful condition that may require dosing interruptions and dose
reductions.
About Metastatic Breast Cancer
Breast cancer is the second leading cause of cancer related
death among women, according to the National Cancer Institute.
During 2012, American Cancer Society estimates that 226,870women
will be diagnosed with breast cancer, while 39,510 women likely
will die from the disease. FDA-approved therapies used to treat
late-stage, refractory breast cancer include capecitabine (Xeloda®)
for patients with breast cancer resistant to paclitaxel and
anthracycline-containing chemotherapy; ixabepilone (Ixempra®) for
patients with late-stage disease after failure of an anthracycline,
taxane and capecitabine; ixabepilone plus capecitabine for patients
with late-stage disease after failure of anthracycline- and
taxane-based chemotherapy; eribulin mesylate (Halaven®) for
patients with metastatic breast cancer who have received at least
two prior chemotherapy regimens for late-stage disease.
Xeloda® is a registered trademark of Genentech, a member of the
Roche Group.
Ixempra® is a registered trademark of Bristol Myers Squibb
Halaven® is a registered trademark of Eisai Pharmaceuticals
Forward Looking Statements
Except for historical information described in this press
release, all other statements are forward-looking. Forward-looking
statements are subject to certain risks and uncertainties inherent
in the Company's business that could cause actual results to vary,
including such risks that regulatory clinical and guideline
developments may change, scientific data may not be sufficient to
meet regulatory standards or receipt of required regulatory
clearances or approvals, clinical results may not be replicated in
actual patient settings, protection offered by the Company's
patents and patent applications may be challenged, invalidated or
circumvented by its competitors, the available market for the
Company's products will not be as large as expected, the Company's
products will not be able to penetrate one or more targeted
markets, revenues will not be sufficient to fund further
development and clinical studies, the Company may not meet its
future capital needs, and its ability to obtain additional funding,
as well as uncertainties relative to varying product formulations
and a multitude of diverse regulatory and marketing requirements in
different countries and municipalities, and other risks detailed
from time to time in the Company's filings with the Securities and
Exchange Commission including its Annual Report on Form 10-K for
the year ended December 31, 2011. Adherex Technologies, Inc.
disclaims any obligation to update these forward-looking statements
except as required by law.
For a more detailed discussion of related risk factors, please
refer to our public filings available at www.sec.gov and
www.sedar.com.
Contacts: Adherex Technologies Inc. Rosty Raykov Chief Executive
Officer (919) 636-5144