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Biomedical engineers and physicians at
CWRU and University Hospitals of Cleveland (UHC) have created
an innovative drug delivery device, a biodegradable polymer rod
smaller than the tip of a lead pencil, to help treat liver cancer.
 "These
rods serve as magic bullets, which will be inserted into a tumor
in the liver using an image-guided minimally invasive procedure.
Each rod is smaller than the tip of a sharpened pencil and provides
dual release kinetics of an anti-tumor agent-an initial burst
of drug therapy followed by sustained release," said Jinming Gao,
the lead researcher and assistant professor in the department
of biomedical engineering at CWRU. "The design of dual-release
kinetics is novel and can potentially allow the most effective
and safest means of local drug therapy."
Gao developed the device with the help
of a $1.2 million grant from the National Cancer Institute, an
arm of the National Institutes of Health. He has collaborated
closely with John Haaga, chair of radiology at UHC. Haaga originally
conceived the concept of combining radiofrequency ablation with
polymer/chemical implantation.
The researchers plan to evaluate the new
device and treatment approach in a rabbit liver tumor model. The
combined procedure is not currently being used in patients. The
research team will compare this new method to single treatment
by radiofrequency ablation, a minimally invasive procedure in
which a needle electrode is inserted through the skin and guided
into a tumor by an imaging method such as computed tomography
(CT) or magnetic resonance imaging (MRI). An electric current
is then introduced through the electrode to elevate the tissue
temperature to 80-90ūC to destroy the tumors. Radiofrequency ablation
research is under Phase II clinical trials at UHC under the leadership
of Haaga and Jonathan Lewin, professor of radiology at CWRU.
"Because not all cancer cells can be killed
by thermal ablation without significant damage to normal cells,
we believe the follow up procedure with local drug therapy is
essential to prevent regrowth of the tumor," said Haaga. "Compared
to conventional systemic chemotherapy, this intratumoral drug
delivery strategy has the potential to reduce the exposure of
normal tissues to the drug while increasing the drug dosage to
the tumor site. Patients can receive much higher local doses of
anti-tumor agents without being at risk for side effects that
can significantly decrease their quality of life."
Each year in the United States an estimated
14,500 new cases of liver and intrahepatic bile duct carcinomas
are diagnosed; the five-year survival rate for these patients
is less than 10 percent. In another 20 to 30 percent of the 160,000
patients diagnosed with colorectal carcinoma, tumors move through
the lymph or blood system. These patients develop liver metastases,
the progressive involvement of which becomes the major or sole
determination of survival.
"The current standard for liver cancer
treatment is tumor resection where the tumor is removed followed
by chemotherapy. But the majority of patients afflicted with primary
or secondary hepatic cancers can't undergo tumor resection due
to factors like age, poor general health and liver function and
advanced cirrhosis where the liver is filed with fibrous tissue,"
Haaga said. "In the last 10 years, image-guided thermal ablation
has emerged as a minimally invasive alternative to tumor resection
for cancers in the liver, pancreas and prostate. Our new device
is designed to work in synergy with image-guided thermal ablation
and looks to offer a bright new combination therapy."
Gao, Haaga and their research team are
establishing a rational approach for the design of the dual-release
millirods, looking into the drug transport and pharmacological
issues involved in controlling the device so it dispenses the
proper concentrations of anti-tumor agents during drug therapy.
"We need to be able to maintain the drug concentration within
the therapeutic window for a prolonged period of time at the boundary
of the tumor tissue," said Gao. "Our current funding from the
National Cancer Institute provides the necessary support and brings
us closer to a viable treatment option."
The researchers are confident that their
polymer device will be of interest to clinical oncologists, radiologists
and others in the medical field that strive to improve the therapeutic
outcome for cancer patients. "Dr. Haaga will lead the clinical
trials at the University Hospitals of Cleveland when we advance
to that stage," Gao said.
In addition to the $1.2 million funding
from the National Cancer Institute, the research also received
a Presidential Technology Development Fund from CWRU to facilitate
the technology transfer from the laboratory to commercialization.
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