Phase I study of transarterial chemoembolization of lung metastases.

Abstract

3602 Background: Lung chemoembolization (via the bronchial or pulmonary artery) is a new treatment option for unresectable and unablatable lung metastases. Methods: 10 patients with unresectable and unablatable lung, endobronchial, or mediastinal metastases, who failed systemic chemotherapy, were enrolled in this single center, single arm, phase I trial. Pulmonary and bronchial angiography was performed in all patients, to determine the blood supply to the lung metastases. Based on the angiographic findings, bronchial or pulmonary artery chemoembolization was performed, using a lipiodol / mitomycin emulsion, followed by spherical particles. Technical success, safety, efficacy, and pharmacokinetics were evaluated. Wilcoxon signed-rank test was used to compare change in size of treated versus untreated tumors. Results: On angiography, all patients had lung metastases that were hypervascular compared to normal lung. 90% of patients had lung metastases supplied by the bronchial artery, and 10% were supplied by the pulmonary artery. Technical success rate of intra-tumoral drug delivery was 100% (95% CI: 76-100%). There were no severe adverse events, and all patients met criteria for discharge 4 hours post procedure. Response rate of treated lesions was 10% by RECIST and 40% by PERCIST. Treated tumors were mostly stable to decreased in size after chemoembolization (median change in size: 0%; IQR: -11% to 2%; mean: -4%), and untreated tumors were mostly increased in size (median change in size: 10%; IQR: 0% to 17%; mean 9%; p= 0.02). Intra-tumoral lipiodol retention at 4-6 weeks was correlated with decreased tumor size and metabolic activity. Pharmacokinetics showed that 45% of the mitomycin dose underwent burst release in 2 minutes, and 55% of the dose was retained intratumorally with a half-life > 5 hours. Initial tumor-to-plasma ratio of mitomycin concentration was 380. Half-life of intratumoral lipiodol retention was 16 days. In vitro experiments showed 50% emulsion separation in 6.2 days, and 50% drug release in 7.1 hours. Conclusions: Lung chemoembolization can safely treat lung, mediastinal, and endobronchial metastases, with minimal systemic toxicity. High intratumoral drug concentrations after chemoembolization can overcome chemoresistance. Clinical trial information: NCT04200417.