938 - Multicenter Trial for Safety and Toxicity of Nanoxel®M in Breast Cancer

Background

This multicenter phase IV study was designed to evaluate the safety, toxicity and quality of life (QoL) of a nanoparticle docetaxel formulation in Breast Cancer Nanoxel®M (Docetaxel-loaded polymeric micelles) were prepared from poly(N-vinylpyrrolidone)-block-poly(D,L-lactide) (PVP-b-PDLLA) using different incorporation methods, additives and drug-loading levels. Taxotere has used polysorbate 80 as unloaded vehicles, which produces hypersensitivitrty and edema. Nanoxel®M could be expected to be improved solubility, reduced toxicity, and reduced hypersensitivity than Taxotere.

Methods

Fifty-five patients with pathological stage II-III breast cancer were enrolled for this trial. Luminal A breast cancer patients were received adjuvant TC (Nanoxel®M 75 mg/m2 plus cyclophosphamide 600 mg/m2) (N = 11). Breast cancer patients with Luminal B, HER2 and triple negative subtype were treated with the adjuvant AC (doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2) followed by Nanoxel®M 75-100 mg/m2 in node positive breast cancer (N = 35). The primary endpoint was safety and toxicity of Nanoxel®M. The secondary endpoints included QoL.

Results

Dose reductions were required for 17 of the 18 patients (94.46%) in Nanoxel®M single 100 mg/m2, 11 of the 27 patients (40.7%) in Nanoxel®M single 75 mg/m2, 9 of the 11 patients (81.8%) in Nanoxel®M 75 mg/m2 combined with cyclophosphamide. Neutropenia was observed in 16 of the 18 patients (88.9%) with grade 4 and in 2 of 18 (11.1%) with grade 3 in Nanoxel®M single 100 mg/m2; in 14 of the 27 patients (51.9%) with grade 4 and in 4 of 27 (14.8%) with grade 3 in Nanoxel®M single 75 mg/m2; and in 7 of the 10 patients (70.08%) with grade 4 and in 1 of 10 (10.0%) with grade 3 in Nanoxel®M 75 mg/m2 combined with cyclophosphamide. The nonhematological toxicities was similar with those of taxotere, which included mucositis, anorexia, nausea, vomiting, diarrhea, and pain. Fluid retention was less than 30%, which was as grade 1-2. Hypersensitivity was developed in one case (1.8%) of Nanoxel®M single 100 mg/m2.

Conclusions

The hematological and nonhematological toxicities of Nanoxel®M were similar with those of taxotere. However solubilizer related toxicities such as fluid retention, hypersensitivity were less frequent than taxotere.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Samyang Biopharm.

Funding

Samyang Biopharm.

Disclosure

All authors have declared no conflicts of interest.