Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
Anticancer Res. 2010 Jan;30(1):167-74.
Bortezomib demonstrates synergism with gemcitabine via a fixed-dose rate (FDR). The aim of this phase I trial in solid tumors was to establish the maximum tolerated dose (MTD) and safety data for this combination.
Twenty-nine patients with a median age of 63 (range 36-84) years and median Karnofsky Performance Status of 90 (range 60-100) were enrolled and treated with bortezomib (1.0 or 1.3 mg/m(2)) on days 1, 4, 8 and 11 and FDR gemcitabine (750, 1,000, or 1,250 mg/m(2)) on days 1 and 8 of each 21-day cycle. Response was evaluated every two cycles.
Dose-limiting toxicities were grade 4 thrombocytopenia and neutropenia and grade 3 liver function test abnormalities. The MTD was bortezomib 1 mg/m2 and FDR gemcitabine 1,250 mg/m(2). The median number of cycles delivered was 3 (range 1-28). There was one partial response and six cases of stable disease. The median duration of response was 8.5 (range 3-20) months.
FDR gemcitabine and bortezomib combination can be delivered effectively with acceptable toxicity.
硼替佐米与吉西他滨联合使用时表现出协同作用，通过固定剂量率（FDR）给药。本研究旨在评估硼替佐米联合 FDR 吉西他滨治疗实体瘤的最大耐受剂量（MTD）和安全性。
共纳入 29 例患者，中位年龄为 63 岁（范围为 36-84 岁），中位 Karnofsky 体能状态为 90 分（范围为 60-100 分）。患者接受硼替佐米（1.0 或 1.3 mg/m2），于第 1、4、8 和 11 天给药，FDR 吉西他滨（750、1000 或 1250 mg/m2），于第 1 和第 8 天给药，每 21 天为 1 个周期。每两个周期评估一次疗效。
剂量限制毒性为 4 级血小板减少和中性粒细胞减少以及 3 级肝功能异常。MTD 为硼替佐米 1 mg/m2 和 FDR 吉西他滨 1250 mg/m2。中位周期数为 3（范围为 1-28）。1 例患者部分缓解，6 例患者疾病稳定。中位缓解持续时间为 8.5 个月（范围为 3-20）。
FDR 吉西他滨联合硼替佐米治疗具有可接受的毒性。
