| Lung cancer
is currently the most prevalent cause of cancer-related
mortality, however, development of new effective
therapies has lagged the treatment advances achieved
with other cancers. Up to 6% of lung cancers are
classified as bronchioalveolar carcinoma (BAC).
This type of tumor commonly presents as a nodule,
or multiple nodules, in the peripheral part of
the lung where it is difficult to diagnose by
conventional, fiber optic bronchoscopy. New developments,
like real-time electromagnetic navigational bronchoscopy
with CT, provide a reliable method to accurately
extend standard bronchoscopy by positioning at
sites of peripheral lung lesions for diagnostic
biopsy. Navigational bronchoscopy also offers
new alternatives for localized chemotherapy of
peripheral lung tumors when combined with the
AeroProbe Intracorporeal Nebulizing Catheter (INC).
By this method, cytotoxic drugs [e.g., cis-platinum
(CDDP) and combinations] in targeted chemotherapy
could be safely and efficiently delivered to peripheral
BAC lesions with increased effectiveness and reduced
potential for pulmonary and systemic toxicities.
This approach remains to be tested in humans with
BAC. Our earlier studies in dogs demonstrate that
after intrabronchial delivery with the INC, at
least 26-fold higher local tissue levels of CDDP
can be achieved in a lung lobe than with IV dosing
and that the localized chemotherapy is well tolerated.
The hypothesis of our current proposal is that
combinations of chemotherapeutic agents that are
effective against BAC cell lines in vitro could
be efficiently and safely delivered by localized
aerosol chemotherapy in experimental animals.
We propose to determine efficacy of CDDP and combinations
against BAC cells in vitro and subsequently assess
tolerance of CDDP and CDDP/combinations administered
directly into the airway by INC in healthy dogs
and rats. The expected result is that highly effective
doses of chemotherapeutic agents could be delivered
to the lungs of these animals without producing
significant pulmonary or systemic toxicity. Our
objective is to obtain tolerance and toxicity
data from two species (dog and rat) in order to
begin the process to obtain IRB and FDA IND approval
for clinical trials of targeted intracorporeal
chemotherapy in humans with BAC. Coupling real-time
electromagnetic navigational bronchoscopy and
localized, aerosol chemotherapy within the lung
could provide a much needed breakthrough in the
treatment of BAC.
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