Phase II trial of bortezomib plus doxorubicin in hepatocellular carcinoma (E6202): a trial of the Eastern Cooperative Oncology Group.
Phase II trial of bortezomib plus doxorubicin in hepatocellular carcinoma (E6202): a trial of the Eastern Cooperative Oncology Group.
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DOI：
10.1007/s10637-014-0111-8
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发表时间：
2014-10
影响因子：
3.4
通讯作者：
Berlin, Jordan
中科院分区：
文献类型：
--
作者：
Ciombor, Kristen K.;Feng, Yang;Benson, Al Bowen, III;Su, Yingjun;Horton, Linda;Short, Sarah P.;Kauh, John Sae Wook;Staley, Charles;Mulcahy, Mary;Powell, Mark;Amiri, Katayoun I.;Richmond, Ann;Berlin, Jordan
评估硼替佐米联合阿霉素治疗晚期肝细胞癌患者的疗效和耐受性，并将蛋白酶体抑制的药效学标志物与反应和生存相关联。实验设计 这项 II 期、开放标签、多中心研究检查了硼替佐米（第 1、4、8、11 天静脉注射 1.3 mg/m2）和阿霉素（第 1、8 天静脉注射 15 mg/m2）在 21 天周期中的疗效。主要终点是客观缓解率。 38 名接受治疗的患者中的最佳缓解为 1 名部分缓解 (2.6%)、10 名 (26.3%) 疾病稳定和 17 名 (44.7%) 疾病进展； 10名患者无法评估。中位 PFS 为 2.2 个月。中位 OS 为 6.1 个月。最常见的 3 至 4 级毒性是高血压、葡萄糖耐受不良、腹水、ALT 升高、高血糖和血栓形成/栓塞。在治疗开始时 IL-6、IL-8、MIP-1α 和 EMSA 升高的患者中，PFS 更差。治疗开始时 IL-8 和 VEGF 升高的患者 OS 较差。如果治疗后血清 MIP-1α/CCL3 的自然对数发生变化，则患者的 OS 会得到改善。 RANTES/CCL5 水平随着治疗显着下降。阿霉素和硼替佐米的联合治疗在肝细胞癌患者中具有良好的耐受性，但未达到主要终点。蛋白酶体抑制标志物的探索性分析表明其可能具有预后和预测作用，应在硼替佐米有效的肿瘤类型中进一步探索。
To evaluate the efficacy and tolerability of bortezomib in combination with doxorubicin in patients with advanced hepatocellular carcinoma, and to correlate pharmaco-dynamic markers of proteasome inhibition with response and survival. Experimental Design This phase II, open-label, multi-center study examined the efficacy of bortezomib (1.3 mg/m2 IV on d1, 4, 8, 11) and doxorubicin (15 mg/m2 IV on d1, 8) in 21-day cycles. The primary endpoint was objective response rate. Best responses in 38 treated patients were 1 partial response (2.6 %), 10 (26.3 %) stable disease, and 17 (44.7 %) progressive disease; 10 patients were unevaluable. Median PFS was 2.2 months. Median OS was 6.1 months. The most common grade 3 to 4 toxicities were hypertension, glucose intolerance, ascites, ALT elevation, hyperglycemia and thrombosis/ embolism. Worse PFS was seen in patients with elevated IL-6, IL-8, MIP-1α and EMSA for NF-κB at the start of treatment. Worse OS was seen in patients with elevated IL-8 and VEGF at the start of treatment. Patients had improved OS if a change in the natural log of serum MIP-1α/CCL3 was seen after treatment. RANTES/CCL5 levels decreased significantly with treatment. The combination of doxorubicin and bortezomib was well-tolerated in patients with hepatocellular carcinoma, but the primary endpoint was not met. Exploratory analyses of markers of proteasome inhibition suggest a possible prognostic and predictive role and should be explored further in tumor types for which bortezomib is efficacious.
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影响因子：
25.7
作者：
Liu, P;Kimmoun, E;Bernuau, D
通讯作者：
Bernuau, D
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：
13.5
作者：
Maeda, Shin;Hikiba, Yohko;Omata, Masao
通讯作者：
Omata, Masao
影响因子：
3.4
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
通讯作者：
Erlichman, Charles
DOI：
10.1007/s10120-005-0315-x
发表时间：
2005-01-01
期刊：
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
影响因子：
--
作者：
Ashizawa, Tatsuto;Okada, Ryosuke;Aoki, Tatsuya
通讯作者：
Aoki, Tatsuya