Development and initial clinical experience with a paclitaxel-coated balloon for the treatment of benign difficult esophageal strictures.

BACKGROUND AND AIMS: Benign esophageal strictures can result in dysphagia and decreased quality of life. A novel drug-coated balloon (DCB) for dilation was developed to dilate strictures while concurrently delivering paclitaxel to reduce recurrence. Initial preclinical histologic and pharmacokinetic (PK) data in addition to first-in-human pilot data are presented.

METHODS

Thirty-nine healthy swine were treated by using 3 different paclitaxel dosing regimens or a bare balloon. Paclitaxel PK elimination profile in plasma and tissue as well as local tissue responses were evaluated. Nine adult human subjects were treated and followed up for up to 2 years with dysphagia scores, safety, and imaging.

RESULTS

In the animal studies, histologic and PK analysis revealed paclitaxel present in treated tissues through 28 days' postprocedure, whereas plasma levels were minimal (1 ng/mL at 155 mg total drug dose). No local or systemic drug toxicity was found. Nine human subjects with an average initial stricture diameter of 6.4 mm and an average Ogilvie Dysphagia Score of 2.2 were treated. No major treatment-related adverse events occurred. The retreatment rate through 2 years was 11%. Five subjects completed 2-year follow-up, with an average 2-year Ogilvie Dysphagia Score of 0. Stricture diameter improved to 19.4 ± .9 mm at 1 year (n = 5).

CONCLUSIONS

The animal studies show that DCB treatment of esophageal mucosa appears safe with paclitaxel still present in tissue after 1 month but at minimal plasma levels. Initial results in humans indicate DCB can be safely applied with clinically relevant increases in esophageal lumen at 1 year with symptomatic improvement. (Clinical trial registration number: NCT03885310.).