SAN DIEGOExternal magnets are being used to guide a novel,
intra-arterially administered chemotherapy delivery vehicle directly
to the tumor site (see illustration
). Scott C. Goodwin, MD, chief of vascular and interventional
radiology, UCLA Medical Center, reported results of an ongoing phase
I/II study of this new regional therapy technique at the annual
scientific meeting of the Society of Cardiovascular &
The product, MTC-DOX, currently being tested in primary liver cancer
patients, is under development by San Diego-based FeRx Incorporated.
It consists of doxorubicin adsorbed to the companys proprietary
Magnetic Targeted Carriers (MTCs).
MTCs are microparticles ranging from 1 to 2 microns in size, composed
of elemental iron and activated carbon, which serve as delivery
vehicles for the site-specific targeting, retention, and sustained
release of the pharmaceutical. The iron component provides the needed
magnetic character, while the carbon component provides carrying
capacity for the drug. The MTCs are manufactured at the companys
facility in Arvada, Colorado.
With MTCs, we hope to get a significant amount of toxic
cancer-killing drugs to remain in the tumor, rather than spreading
throughout the body, thereby reducing side effects such as nausea and
hair loss, Dr. Goodwin said. Our early results make us
hopeful that site-specific drug delivery with MTCs will improve
response rates of anticancer drugs, while at the same time reducing
the complications of chemotherapy.
Dr. Goodwin presented data on 14 patients with advanced
hepatocellular carcinoma who received a single dose of MTC-DOX via
intra-arterial infusion. Doses ranged from 3 mg doxorubicin/37.5 mg
MTCs to 18 mg doxorubicin/225 mg MTCs.
The drug solution is mixed with the vialed MTCs just prior to
administration. The agent is then given via a catheter placed in a
subsegmental branch of a hepatic artery feeding the tumor to be treated.
In this study, delivery was targeted to a single lesion in a specific
hepatic segment, using a small, externally positioned magnet (5
kilogauss) to creat a localized magnetic field within the body over
the tumor site. The physical force created by the magnetic field
induces transport (extravasation) of the MTCs through the vascular
wall (see Figure 1).
The external magnet remains in place for about 15 minutes after
dosing. Upon removal of the magnet, the MTCs do not recirculate but
are retained in the tissue where the drug then desorbs from the MTCs,
leading to sustained release of the particles at the desired site.
Angiography was performed before and after dosing, and patients
underwent baseline and 28-day follow-up CT and magnetic resonance
(MR) images to document tumor size and number of lesions as well as
MTC particle distribution. In patients with multiple lesions, the
non-targeted lesions were used as controls.
Dr. Goodwin reported that MR im-ages have shown deposition of the
particles solely in the selected site, as seen in Figures
2 and 3. The MTC-DOX is seen as darkened areas within the liver.
This is due to the iron component of MTC, which acts as a negative
contrast agent in MR imaging.
After 28 days, MRI results show that the particles remain in
the targeted site with no redistribution, Dr. Goodwin said.
Angiography has shown no significant arterial embolization (see the illustration
), and no study-related deaths have occurred.
This preliminary report shows that of the first 14 patients, one
patient had a partial response (greater than 50% tumor reduction),
and two patients had a minor response (25% to 50% tumor reduction).
Five patients had stable disease, and six had disease progression.
FeRx plans to initiate phase II trials of MTC-DOX later this year to
further assess dosing, safety, and efficacy in patients with primary
liver cancer, and also plans to expand the development program to
other solid tumors.