Phase I study of nanoparticle albumin-bound paclitaxel, carboplatin and trastuzumab in women with human epidermal growth factor receptor 2-overexpressing breast cancer

Abstract

Abstract. Although the concurrent use of anthracycline-containing chemotherapy and taxane with trastuzumab are considered the treatment of choice for the primary systemic therapy of human epidermal growth factor receptor 2 (HER2)-overexpressing early breast cancer, non-anthracycline regimens, such as concurrent administration of docetaxel and carboplatin with trastuzumab, exhibited similar efficacies in a previous study. In addition, tri-weekly treatment with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) resulted in significantly higher response rates and a favorable safety profile compared with standard paclitaxel for metastatic breast cancer patients in another phase III study. Based on these results, a phase I study of combination therapy with nab-paclitaxel, carboplatin and trastuzumab was planned, in order to estimate its efficacy and safety for HER2-overexpressing locally advanced breast cancer. The present study was designed to determine the dose-limiting toxicity (DLT), maximum tolerated dose and recommended dose of this combination treatment in women with HER2-overexpressing locally advanced breast cancer. The starting dose of nab-paclitaxel was 220 mg/m 2 (level 1), and the dose was escalated to 260 mg/m 2 (level 2). Nab-paclitaxel was administered with carboplatin (area under the curve, 6 mg/ml/min) and trastuzumab tri-weekly. A total of 6 patients were enrolled. Although no DLT was observed during the first cycle, 4 patients developed grade 4 thrombocytopenia, 2 had grade 4 neutropenia and 3 exhibited a grade 4 decrease in hemoglobin levels. In the present phase I study, although no patients experienced DLTs, this regimen was associated with severe hematological toxicities and it was not well tolerated. However, considering the high efficacy and lower risk of cardiotoxicity and secondary carcinogenesis with taxane, platinum and trastuzumab combination therapy, further evaluation of another regimen including weekly administration or a more accurate dose setting should be conducted.Phase I study of nanoparticle albumin-bound paclitaxel, carboplatin and trastuzumab in women with human epidermal growth factor receptor 2-overexpressing breast cancer

Drug Combinations in Breast Cancer Therapy

“…No DLT was observed during the first cycle, however, 4 patients developed grade 4 thrombocytopenia, 2 had grade 4 neutropenia and 3 exhibited a grade 4 decrease in hemoglobin levels. The study concluded that although no DLTs were observed in the first cycle of the treatment, hematological toxicity (anemia) presented difficulties with continuity [112].…”

The past, present, and future of breast cancer models for nanomedicine development

“…Furthermore, Abraxane® promoted higher tumor accumulation of paclitaxel (~33%), inhibited elimination (4-fold decrease) [37] , and demonstrated a superior overall response rate (34%) compared to paclitaxel (19%) in patients with advanced breast cancer [38] , [58] . Importantly, combination therapies of Abraxane® with conventional chemotherapeutic agents and targeted therapies have also demonstrated safety and superior efficacy compared to single therapies in clinical trials [52] , [53] . Lipusu® (China, 2003) was the first liposomal formulation of paclitaxel approved for the treatment of non-small lung cancer, ovarian, and breast cancer [41] , [42] , [51] , [56] .…”

Nanomedicines Targeting Heat Shock Protein 90 Gene Expression in the Therapy of Breast Cancer

“…In conclusion to different clinical trials, Abraxane showed more efficient results over solvent-based paclitaxel, and can be used with chemotherapy and other targeted therapies. [30] Passive and active targeting of nano-carriers in breast cancer treatment…”