An international, multicenter phase II trial of bortezomib in patients with hepatocellular carcinoma.
An international, multicenter phase II trial of bortezomib in patients with hepatocellular carcinoma.
复制标题
DOI：
10.1007/s10637-010-9532-1
复制
发表时间：
2012-02
影响因子：
3.4
通讯作者：
Erlichman, Charles
中科院分区：
文献类型：
--
作者：
Kim, George P.;Mahoney, Michelle R.;Szydlo, Daniel;Mok, Tony S. K.;Marshke, Robert;Holen, Kyle;Picus, Joel;Boyer, Michael;Pitot, Henry C.;Rubin, Joseph;Philip, Philip A.;Nowak, Anna;Wright, John J.;Erlichman, Charles
（PS-341，VELCADE®）是26 S蛋白酶体的选择性抑制剂，26 S蛋白酶体是泛素蛋白酶体途径的组成部分。这项II期研究评估了硼替佐米在不可切除的肝细胞癌（HCC）患者中的活性和耐受性。主要终点是确认的肿瘤缓解率（RR），次要终点包括缓解持续时间、疾病进展时间、生存期和毒性。治疗包括在每个21天治疗周期的第1、4、8和11天IV推注硼替佐米1.3 mg/m2。资格包括：既往未接受全身化疗，ECOG PS 0-2，Child-Pugh A或B，保留血液学、肝脏和神经功能;允许既往接受肝脏定向治疗。35例患者入组并接受了中位2个周期的治疗（范围1-12）。总体而言，分别有24例和4例患者发生了最大严重程度为3级和4级的不良事件（AE）。未发生治疗相关死亡。仅血小板减少症（11%）见于超过10%的患者。1例患者获得部分缓解，治疗期间持续13周，11.6个月后进展; 2例患者接受治疗超过6个月。中位进展时间为1.6个月，中位生存期为6.0个月。这项国际多中心试验评估了硼替佐米作为单药治疗不可切除的HCC患者的效果。而且，尽管缺乏显著的活性，但该报告可作为未来开发包括硼替佐米在内的双重生物方法的基线临床经验。
(PS-341, VELCADE®) is a selective inhibitor of the 26S proteasome, an integral component of the ubiquitinproteasome pathway. This phase II study evaluated the activity and tolerability of bortezomib in unresectable hepatocellular carcinoma (HCC) patients. The primary endpoint was confirmed tumor response rate (RR) with secondary endpoints including duration of response, time to disease progression, survival and toxicity. Treatment consisted of bortezomib, 1.3 mg/m2 IV bolus on days 1, 4, 8, and 11 of each 21-day treatment cycle. Eligibility included: no prior systemic chemotherapy, ECOG PS 0-2, Child-Pugh A or B, preserved hematologic, hepatic and neurologic function; prior liver-directed therapy was permitted. Thirty-five patients enrolled and received a median of 2 cycles of treatment (range 1–12). Overall, 24 and 4 patients had a maximum severity of grade 3 and 4 adverse events (AEs), respectively. No treatment related deaths occurred. Only thrombocytopenia (11%) was seen in greater than 10% of patients. One patient achieved a partial response, lasting 13 weeks during treatment and progressed 11.6 months later; two patients received treatment for greater than 6 months. Median time-to-progression was 1.6 months and median survival was 6.0 months. This international, multicenter trial evaluated bortezomib as monotherapy in unresectable HCC patients. And, despite the lack of significant activity, this report serves as a baseline clinical experience for the development of future dual biologic approaches including bortezomib.
登录
查看更多内容
影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
影响因子：
4.2
作者：
El-Serag, Hashem B.
通讯作者：
El-Serag, Hashem B.
影响因子：
45.3
作者：
Abou-Alfa, Ghassan K.;Schwartz, Lawrence;Saltz, Leonard B.
通讯作者：
Saltz, Leonard B.
影响因子：
2.2
作者：
Bold, RJ;Virudachalam, S;McConkey, DJ
通讯作者：
McConkey, DJ