The treatment goals for metastatic breast cancer (MBC) are prolonging survival and improving the quality of life. Eribulin, a non-taxane tubulin inhibitor, demonstrated improved survival in previous studies and also showed mild toxicity when used in late-line therapy for MBC. We conducted a phase II study to investigate the efficacy of eribulin mesylate as the first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative MBC. This was a phase II, open-label, single-arm, multicenter trial conducted in Japan. Patients with HER2-negative MBC received intravenous eribulin (1.4 mg/m2 on days 1 and 8 of each 21-day cycle). The primary efficacy outcome was overall response rate (ORR). Secondary outcomes included time to treatment failure, progression-free survival (PFS), overall survival (OS), and safety. A total of 35 patients were enrolled and received a median of 8 (range 1–21) cycles of eribulin therapy. ORR and clinical benefit rate were 54.3 and 62.9 %, respectively. Median PFS was 5.8 months and median OS was 35.9 months. Grade 3 or 4 neutropenia was observed in 63 % of patients. The majority of non-hematological adverse events were mild in severity. The present trial demonstrated that eribulin has antitumor activity comparable with other key established cytotoxic agents with acceptable safety and tolerability. Thus, eribulin as first-line chemotherapy might be beneficial for patients with HER2-negative MBC.

XELOX plus bevacizumab is an effective treatment strategy and has a manageable tolerability profile when administered to Japanese patients with metastatic colorectal cancer (mCRC). In this study, we retrospectively reviewed cases in which XELOX plus bevacizumab were administered in order to evaluate its efficacy and safety in clinical practice. In total, 40 patients with mCRC who presented at Fuchu Hospital received XELOX plus bevacizumab as a first-line treatment between September, 2009 and April, 2012. Eligible patients had histologically confirmed mCRC. XELOX consisted of a 2-h intravenous infusion of oxaliplatin 130 mg/m on day 1 plus oral capecitabine 1,000 mg/m twice daily for 2 weeks of a 3-week cycle. Overall survival (OS) and survival benefit were analyzed when patients continued with XELOX plus bevacizumab beyond disease progression. The median progression-free survival (PFS) was 290 days [95% confidence interval (CI): 222-409 days] and the median OS was 816 days (95% CI: 490 days-not calculated). The response rate (RR; complete plus partial response) was 67.5%, and the disease control rate (RR plus stable disease) was 90%. The most common adverse events observed following administration of XELOX plus bevacizumab were neurosensory toxicity (82.5%), anorexia (50%), hypertension (45%) and a decrease in the platelet count (40%). The most common grade 3/4 adverse events were neurosensory toxicity (15%) and fatigue (15%). In conclusion, XELOX plus bevacizumab may be considered a routine first-line treatment option for patients with mCRC. Notably, the combination of capecitabine and bevacizumab was safe with an acceptable toxicity profile and induced a significant rate of disease control.

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

Nab-PTX 175 mg/m/3wks regimen has a good safety profile and less frequent CIPN. This regimen can contribute to the strategy of MBC treatment.

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