Phase I Dose-Escalation Study Combining Irinotecan-Loaded Drug-Eluting Bead Chemoembolization with Yttrium-90 Glass Microspheres Radioembolization in Colorectal Liver Metastases (DEBIR90Y)

Purpose

To find the maximum tolerated dose (MTD) of yttrium-90 (90Y) glass microspheres, with drug-eluting beads preloaded with irinotecan (DEBIRI) in patients with colorectal liver metastases (CRLMs). Materials and Methods: In this prospective study, participants with bilobar, unresectable, liver-dominant CRLM progressing after first-line systemic therapy received sequential bilobar 90Y glass microsphere radioembolization at increasing dose levels (60-Gy, 80-Gy, and 100-Gy perfused normal liver absorbed doses), followed by DEBIRI, using a 3 + 3 dose-escalation design. The primary endpoint was MTD determination. Secondary endpoints included objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST), (serious) adverse events ([S]AEs), carcinoembryonic antigen (CEA) response, conversion to resection, and overall survival. Descriptive statistics and independent t-tests were applied.