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.