Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Leuk Lymphoma. 2013 Mar;54(3):497-502. doi: 10.3109/10428194.2012.722215. Epub 2012 Sep 11.
Preclinical studies suggest that bortezomib, through inhibition of nuclear factor-κB (NF-κB) activation, may enhance the effects of radioimmunotherapy. This phase I trial was designed to determine the maximum tolerated dose (MTD) of weekly bortezomib induction combined with Y-90-ibritumomab tiuxetan followed at the time of count recovery by weekly bortezomib consolidation in patients with relapsed/refractory follicular or transformed non-Hodgkin lymphoma. Grade 3 or 4 toxicities were observed in eight of nine treated patients, and all but one of these toxicities were hematologic. One patient had grade 3 cardiotoxicity. A dose limiting toxicity (DLT) of grade 4 thrombocytopenia was observed in two of three patients treated with bortezomib at 1.6 mg/m(2), resulting in a MTD of 1.3 mg/m(2). The overall response rate was 89% (two complete response [CR], six partial response [PR], one stable disease [SD]), with a median progression-free survival of 6.5 months (range: 3-22.5+ months). A phase II trial at the MTD is under way to better define the toxicity and effectiveness of this regimen.
临床前研究表明硼替佐米通过抑制核因子-κB（NF-κB）的激活，可能增强放射免疫治疗的效果。本研究为 I 期临床试验，旨在确定每周硼替佐米诱导治疗联合 Y-90-碘替曲肽，在血细胞计数恢复时给予每周硼替佐米巩固治疗，用于治疗复发/难治性滤泡性或转化性非霍奇金淋巴瘤患者的最大耐受剂量（MTD）。9 例患者中有 8 例观察到 3 级或 4 级毒性，除 1 例外均为血液学毒性。1 例患者发生 3 级心脏毒性。硼替佐米 1.6mg/m2 治疗的 3 例患者中有 2 例出现 4 级血小板减少症（DLT），导致 MTD 为 1.3mg/m2。总缓解率为 89%（2 例完全缓解[CR]，6 例部分缓解[PR]，1 例稳定疾病[SD]），中位无进展生存期为 6.5 个月（范围：3-22.5+个月）。目前正在进行 MTD 下的 II 期临床试验，以更好地确定该方案的毒性和有效性。
