Sequential intra-arterial infusion of 90Y-labeled microspheres and Mitomycin C in chemo refractory liver metastatic breast cancer patients: a single centre pilot study.

Abstract

Objectives: To evaluate the safety and feasibility of intra-arterial Mitomycin C (MMC) infusion after radioembolization with microspheres labelled with yttrium-90 (⁹⁰Y) in liver metastatic breast cancer (LMBC) patients.

Material and Methods: This prospective pilot study included LMBC patients from 2012-2018. Patients first received ⁹⁰Y, where after response was evaluated by MRI, ¹⁸F-FDG PET/CT and laboratory tests. After exclusion of progressive disease, MMC infusion was administered 8 weeks later in different dose cohorts; A: 6mg 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 ⁹⁰Y 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 ⁹⁰Y consisting of a gastrointestinal ulcer whereby prolonged hospitalization was needed.

Conclusion: Sequential treatment of intra-arterial infusion of MMC after ⁹⁰Y was feasible in 75% of the patients when MMC is administered in different escalating dose cohorts. However, caution is needed to prevent reflux after ⁹⁰Y in LMBC patients.