Shinichiro Kubo

The efficacy and feasibility of dose-dense sequential chemotherapy for Japanese patients with breast cancer

BackgroundPerioperative dose-dense chemotherapy (DDCT) with granulocyte-colony stimulating factor (G-CSF) prophylaxis is a standard treatment for patients with high-risk breast cancer. The approval of this approach in Japan led to the widespread adoption of DDCT, despite limited efficacy and safety data among Japanese patients. We evaluated the efficacy and safety of neoadjuvant DDCT for Japanese patients with breast cancer.MethodsThis prospective, multicenter, phase II study evaluated 52 women with operable human epidermal growth factor receptor 2-negative breast cancer and axillary lymph node metastasis. Neoadjuvant DDCT (adriamycin plus cyclophosphamide or epirubicin plus cyclophosphamide followed by paclitaxel) was administrated every 2 weeks with G-CSF support. The study endpoints were the rates of pathological complete response (pCR), febrile neutropenia, treatment completion, toxicities, and the relative dose intensity (RDI).ResultsThe pCR rate was 21.9% (9/41) and the triple-negative (TN) subtype was significantly associated with a high pCR rate (triple-negative: 53.3% vs. luminal A: 7.7% and luminal B: 0%; pu2009=u20090.003). The treatment completion rate was 80.8% (42/52) and the average RDI was 98.9%. Most adverse events were manageable and tolerable. Six patients (11.5%) developed febrile neutropenia. Grade 3–4 adverse events were slightly more common among older patients (57%) with a low protocol completion rate (≥u200965 years: 42.9% vs. <65 years: 86.7%, pu2009=u20090.0062).ConclusionThe pCR rate for DDCT was similar to that of standard chemotherapy, although it was remarkably effective for the TN subtype. DDCT may be feasible for Japanese patients with breast cancer although caution is needed for older patients.

First synthesis of (±)-myristicyclin A

ABSTRACT The first synthesis of myristicyclin A, which was isolated from the Papua New Guinean plant Horsfieldia spicata, is described. The synthesis features acid-mediated hydroarylation reaction to form a dihydrocoumarin moiety, construction of the 2,8-dioxabicyclo[3.3.1]nonane skeleton under acidic conditions, and regioselective Friedel-Crafts acylation at a later stage. GRAPHICAL ABSTRACT The first synthesis of (±)-myristicyclin A (1) was accomplished in eight steps and overall 18% yield.