固定剂量率吉西他滨联合硼替佐米治疗晚期实体瘤的 I 期临床试验。
Phase I trial of fixed-dose rate gemcitabine in combination with bortezomib in advanced solid tumors.
机构信息
Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
出版信息
Anticancer Res. 2010 Jan;30(1):167-74.
BACKGROUND
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.
PATIENTS AND METHODS
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.
RESULTS
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.
CONCLUSION
FDR gemcitabine and bortezomib combination can be delivered effectively with acceptable toxicity.
背景
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。
方法
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。
结果
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）。
结论
FDR 吉西他滨联合硼替佐米治疗具有可接受的毒性。
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