SESSION TITLE: Novel Bronchoscopic Treatments
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Tuesday, October 29, 2013 at 04:30 PM - 05:30 PM
PURPOSE: Direct injection of anti-cancer agents into central airway malignancy to maintain airway patency is a palliative intervention option for patients who have developed respiratory failure and/or post obstructive pneumonia. We had reported results of a preliminary porcine safety study using a new endobronchial injectable catheter through flexible bronchoscope working channel. Pharmacokinetics must be evaluated in the in vivo setting prior to the human application. The purpose of the study was to assess the pharmacokinetics of pig bronchi one week after varying concentrations of paclitaxel (PTX).
METHODS: The Blowfish Catheter (Mercator MedSystems, Inc.) deploys into the airway wall through flexible bronchoscope. PTX diluted in saline with 20% contrast was infused through the needle in 1 ml volume into each treatment site. PTX concentrations were 0.05mg/ml (low dose), 0.5mg/ml (medium dose) and 2.5mg/ml (high dose), respectively. Blood samples were collected immediately after the injection and at 1, 4, 24, 48 hours and 7 days. PTX bronchial tissue concentration was determined at day 7 using an HPLC analysis.
RESULTS: All 3 animals tolerated the procedure well and were sacrificed at day 7 per protocol. PTX plasma concentration was detected immediately after all infusions and decreased over time. In the low and medium dose pigs PTX plasma concentrations were below the method’s Limit of Quantitation at 7 days. In the high dose animal, even at 7 days, the PTX plasma concentration was at detectible levels (0.124 ng/mL). The AUC(0-48h) was 18.53 ng* h/ml (low), 255.98 ng* h/ml (medium), AUC(0-168h) 740.51 ng* h/ml (high), respectively. Average PTX tissue concentrations in the injection site was 35±15 nM (low), 86±33 nM (medium), and 94±67nM (high), respectively.
CONCLUSIONS: Systemic PTX levels were minimal and PTX tissue concentrations were maintained at cancer-inhibiting levels up to 7 days in all three doses studied.
CLINICAL IMPLICATIONS: Direct anti-cancer drug injection with this catheter may enable treating malignant central airway obstruction by localized delivery directly into the tumor without systemic adverse effects of the anti-cancer agents.
DISCLOSURE: Plamena Entcheva-Dimitrov: Employee: Plamena Entcheva-Dimitrov is independent consultant of Mercator MedSystems, Inc. Kirk Seward: Shareholder: Dr. Kirk Seward is a shareholder of Mercator MedSystems, Inc., Employee: Kirk Seward is President and Chief Technology Officer of Mercator MedSystems, Inc, Fiduciary position (of any organization, association, society, etc, other than ACCP: Kirk Seward is on the Board of Directors of Mercator MedSystems, Inc., Grant monies (from sources other than industry): The project described was supported by Award Number R42CA141907 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health., Other: Product/procedure/technique that is considered research and is NOT yet approved for any purpose. The Blowfish Micro-Infusion Catheter is an investigational product; not yet cleared for marketing by the FDA. The following authors have nothing to disclose: Hisashi Tsukada, Samaan Rafeq, Armin Ernst
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