A Dose-Escalating Pilot Study (NCT03017404) of Pegylated Liposomal Doxorubicin and Cyclophosphamide, Followed by Docetaxel Administration as a Neoadjuvant Chemotherapy Regimen in Patients with Locally Advanced Breast Cancer.

BACKGROUND: Pegylated liposomal doxorubicin (PEG-LD) has a comparable efficacy but a distinct toxicological profile compared with free doxorubicin. The use of PEG-LD and cyclophosphamide followed by docetaxel regimen as neoadjuvant chemotherapy has not been well established.

OBJECTIVES: We aimed to assess the maximum tolerated dose (MTD) and toxicity of this regimen in patients with locally advanced breast cancer.

METHODS: A total of 19 patients were enrolled in this trial. In the initial treatment plan, patients were given PEG-LD at 35, 40, 45, or 50 mg/m2 on day 1 during the first four cycles, and cyclophosphamide was administered at a dose of 600 mg/m2. During the last four cycles, docetaxel was administered at 75 mg/m2 on day 1 of a 21-day scheme.

RESULTS: The MTD was 40 mg/m2 PEG-LD and 600 mg/m2 cyclophosphamide administered on day 1 of a 21-day cycle. Dose-limiting toxicity, grade 3 hand-foot syndrome, was observed in one patient during level 2 and three patients during level 3. Other side effects included neutropenia, anemia, stomatitis, rash, nausea/vomiting, alopecia, transaminase elevation, and cardiotoxicity. The pathological complete response rate was 21.1%.

CONCLUSIONS: Our study demonstrated that combination of 40 mg/m2 PEG-LD and 600 mg/m2 cyclophosphamide, followed by 75 mg/m2 docetaxel on day 1 of a 21-day scheme, was an efficacious and well-tolerated neoadjuvant regimen for patients with locally advanced breast cancer.