Sequential Intra-arterial Infusion of (90)Y-resin Microspheres and Mitomycin C in Chemo Refractory Liver Metastatic Breast Cancer Patients: a Single Centre Pilot Study

BACKGROUND: The aim of the study was to evaluate the safety and feasibility of intra-arterial mitomycin C (MMC) infusion after selective internal radiation therapy (SIRT) using Yttrium-90 ((90)Y) resin microspheres in liver metastatic breast cancer (LMBC) patients. PATIENTS AND METHODS: The prospective pilot study included LMBC patients from 2012–2018. Patients first received infusion of (90)Y resin microspheres, after 6–8 weeks response to treatment was assessed by MRI, (18)F-FDG PET/CT and laboratory tests. After exclusion of progressive disease, MMC infusion was administrated 8 weeks later in different dose cohorts; A: 6 mg in 1 cycle, B: 12 mg in 2 cycles, C: 24 mg in 2 cycles and D: maximum of 72 mg in 6 cycles. In cohort D the response was evaluated after every 2 cycles and continued after exclusion of progressive disease. Adverse events (AE) were reported according to CTCAE version 5.0. RESULTS: Sixteen patients received (90)Y treatment. Four patients were excluded for MMC infusion, because of extra hepatic disease progression (n = 3) and clinical and biochemical instability (n = 1). That resulted in the following number of patient per cohort; A: 2, B: 1, C: 3 and D: 6. In 4 of the 12 patients (all cohort D) the maximum dose of MMC was adjusted due biochemical toxicities (n = 2) and progressive disease (n = 2). One grade 3 AE occurred after (90)Y treatment consisting of a gastrointestinal ulcer whereby prolonged hospitalization was needed. CONCLUSIONS: Sequential treatment of intra-arterial infusion of MMC after (90)Y SIRT was feasible in 75% of the patients when MMC was administrated in different escalating dose cohorts. However, caution is needed to prevent reflux after (90)Y SIRT in LMBC patients.