A single-center, self-controlled, phase I clinical trial of mitoxantrone hydrochloride injection for lymph tracing for sentinel lymph node identification of breast cancer.

Background: Mitoxantrone hydrochloride injection for lymph tracing (MHI) is a novel lymphatic tracer for sentinel lymph node (SLN) in patients with early breast cancer but exhibited remarkable liver, kidney, and hematologic toxicities in previous studies. Here, the pharmacokinetics and pharmacodynamics profiles of MHI were evaluated to surmise safety and tolerability.

Methods: Phase 1 open-label, single center, and dose escalation study was performed. Ten patients with invasive breast cancer received 0.5, 1.0, or 2.0 mL of MHI into the breast tissues surrounding the tumor for lymphatic mapping. All of these patients were injected with 2 mCi nuclide-labeled sulfur colloid as a self-control 24 to 48 hours before surgery. Safety was assessed by the incidence of adverse events graded by the National Cancer Institute Common Terminology Criteria, version 4.0.3 (CTCAE4.0.3). Blood samples for pharmacokinetic analyses were collected before and after administration at 15, 30, 60, 120, and 240 min of the injection of MHI.

Results: Up to the cutoff date of the study (Aug 8, 2018), no dose-limiting toxic effects or obvious allergic reactions were observed. Only one case of an adverse event was certainly related to MHI, where it caused blue discoloration of the local skin over the injection site after the operation, but this stain gradually went away. The peak level of MHI was achieved after 15-30 min post injection and completely eliminated from the plasma after 60 min. There were no significant differences in the number of lymph nodes detected by MHI and radioactive colloid. Only one patient with lymph node macrometastases had no SLN detected by either the radioactive colloid or the MHI.

Conclusions: At a dose of up to 2.0 mL, MHI was well tolerated and safe for conducting SLN biopsies in patients with breast cancer. Although there was a case with blue discoloration of the local skin over the injection site after the operation, and remained for a short period of time, but the overall safety was acceptable. Here, we approached a novel SLN tracing slant; however, more investigations of MHI should be performed for further evaluations. (Chinadrugtrials.org.cn number: CXHL1301201, Date of registration: October 12, 2015.).