PubMedJournal of vascular and interventional radiology : JVIR2026-07-17
Phase I Dose-Escalation Study Combining Irinotecan-Loaded Drug-Eluting Bead Chemoembolization with Yttrium-90 Glass Microspheres Radioembolization in Colorectal Liver Metastases (DEBIR90Y).
Ho Li Shen LS, Alsultan Ahmed A, Smits Maarten L J MLJ, Koopman Miriam M et al.
To find the maximum tolerated dose (MTD) of yttrium-90 (90Y) glass microspheres, with irinotecan-loaded drug-eluting beads (DEBIRI) in patients with colorectal liver metastases (CRLM).
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, 100 Gy perfused normal liver absorbed dose), followed by DEBIRI, using a 3+3 dose-escalation design. The primary endpoint was MTD determination. Secondary endpoints included objective response rate (ORR) by RECIST 1.1 and PERCIST, (serious) adverse events ((S)AEs), carcinoembryonic antigen response (CEA), conversion to resection, and overall survival. Descriptive statistics and independent t-tests were applied.
Twelve participants were enrolled. One dose-limiting toxicity (DLT; possible treatment-related fatal liver failure) occurred in the 80 Gy cohort, with no additional DLTs after cohort expansion (n=6). At 100 Gy, two additional DLTs (probable and possible treatment-related fatal liver failure) occurred, establishing 80 Gy as the MTD when combined with full-dose DEBIRI. Eighty treatment-related (S)AEs occurred, most commonly increased gamma-glutamyl transferase (12/12, grade 1-3) and abdominal pain (10/12, grade 1-2). ORR was 9% (RECIST) and 18% (PERCIST). Index lesion response rates were 20% (RECIST) and 35% (PERCIST). CEA response occurred in 42%.
In this phase I study in patients with liver-dominant colorectal metastases, receiving a combination of yttrium-90 radioembolization with DEBIRI combined with DEBIRI, the maximum tolerated dose was 80 Gy. Considerable treatment-related toxicity was observed and objective response rates were limited.