| Lung cancer
is a world-wide menace causing enormous suffering,
misery, and death. Bronchioalveolar carcinoma
(BAC) is one type of lung cancer that typically
presents as a single or multiple nodules in the
outer areas of the lung, where it is hard to diagnose
and difficult to treat effectively. The ultimate
goal of our proposed study is to employ newly
emerging technologies to diagnose and treat BAC
effectively. The new technologies are real time,
electromagnetic, navigational bronchoscopy and
the intracorporeal nebulizing catheter (INC) system
for aerosol delivery of chemotherapy to the lung.
The electromagnetic bronchoscopy guides the bronchoscopist
to a lesion in the peripheral part of the lung
and the INC is then used through the bronchoscope
channel to deliver targeted chemotherapy using
single or combined anti-cancer drugs. This new
combined method of lung cancer therapy offers
many potential advantages over existing treatments.
Higher levels of the active anti-cancer drugs
can be safely and quickly achieved in the lung
directly where the tumor is growing than is possible
by conventional delivery methods. This non-invasive
technique also allows concurrent treatment of
lung tumors at multiple sites and avoids exposure
of normal lung tissue to potentially toxic drugs.
Moreover, development of the systemic side-effects
of chemotherapy, such as, nausea, hair loss, or
bone marrow suppression could be reduced or eliminated
by such localized chemotherapy.
In our earlier studies, we have successfully
targeted cisplatin chemotherapy with the INC inserted
through the bronchoscope channel into the lungs
of healthy dogs. These studies showed that after
intrabronchial delivery with INC, almost 26-fold
higher levels of the drug were achieved in the
lung tissue, whereas, the levels in the blood
were 19-fold lower than those achieved with a
similar dose given by the conventional intravenous
route. Moreover, there was almost no systemic
toxicity after administration of serially increasing
doses of cisplatin administered through the airway
with the INC. In the current proposal, we plan
to establish tolerance and safety in at least
two experimental animal species. Such studies
are needed before this technique of administering
localized chemotherapy can be approved for use
in humans. We propose to first identify the most
important active drug combinations by testing
against human BAC cells in tissue culture. Next,
we will use the most effective chemotherapy agents
in combination by targeted, aerosol delivery of
chemotherapy into the lungs of healthy experimental
animals. If this route of delivery is well tolerated,
these novel studies would help in identifying
a dosing regimen (drug combination and dose) that
could be employed for clinical trials in patients
with BAC. The team of investigators for the project
combines the expertise of experienced basic science
and clinical investigators, so that the results
of the proposed studies can be readily translated
to the bedside.
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