医学
伊立替康
替莫唑胺
中性粒细胞减少症
恶心
内科学
临床研究阶段
耐火材料(行星科学)
人口
胃肠病学
肿瘤科
外科
药理学
临床试验
化疗
癌症
结直肠癌
物理
环境卫生
天体生物学
作者
Steven G. DuBois,Araz Marachelian,Elizabeth Fox,Rachel A. Kudgus,Joel M. Reid,Susan Groshen,Jemily Malvar,Rochelle Bagatell,Lars M. Wagner,John M. Maris,Randall A. Hawkins,Jesse Courtier,Hollie Lai,Fariba Goodarzian,Hiroyuki Shimada,Scarlett Czarnecki,Denice Tsao‐Wei,Katherine K. Matthay,Yaël P. Mossé
标识
DOI:10.1200/jco.2015.65.4889
摘要
Alisertib is an oral Aurora A kinase inhibitor with preclinical activity in neuroblastoma. Irinotecan and temozolomide have activity in patients with advanced neuroblastoma. The goal of this phase I study was to determine the maximum tolerated dose (MTD) of alisertib with irinotecan and temozolomide in this population.Patients age 1 to 30 years with relapsed or refractory neuroblastoma were eligible. Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m(2) per day on days 1 to 7 along with irinotecan 50 mg/m(2) intravenously and temozolomide 100 mg/m(2) orally on days 1 to 5. Dose escalation of alisertib followed the rolling six design. Samples for pharmacokinetic and pharmacogenomic testing were obtained.Twenty-three patients enrolled, and 22 were eligible and evaluable for dose escalation. A total of 244 courses were administered. The MTD for alisertib was 60 mg/m(2), with mandatory myeloid growth factor support and cephalosporin prophylaxis for diarrhea. Thrombocytopenia and neutropenia of any grade were seen in the majority of courses (84% and 69%, respectively). Diarrhea in 55% of courses and nausea in 54% of courses were the most common nonhematologic toxicities. The overall response rate was 31.8%, with a 50% response rate observed at the MTD. The median number of courses per patient was eight (range, two to 32). Progression-free survival rate at 2 years was 52.4%. Pharmacokinetic testing did not show evidence of drug-drug interaction between irinotecan and alisertib.Alisertib 60 mg/m(2) per dose for 7 days is tolerable with a standard irinotecan and temozolomide backbone and has promising response and progression-free survival rates. A phase II trial of this regimen is ongoing.
科研通智能强力驱动
Strongly Powered by AbleSci AI