Nuclear factor-kappa B pathway and response in a phase II trial of bortezomib and docetaxel in patients with recurrent and/or metastatic head and neck squamous cell carcinoma
Nuclear factor-kappa B pathway and response in a phase II trial of bortezomib and docetaxel in patients with recurrent and/or metastatic head and neck squamous cell carcinoma
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DOI：
10.1093/annonc/mdp390
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发表时间：
2010-04-01
影响因子：
50.5
通讯作者：
Murphy, B. A.
中科院分区：
文献类型：
--
作者：
Chung, C. H.;Aulino, J.;Murphy, B. A.
背景：我们之前的研究表明，核因子 kappa B (NF-kappa B) 信号通路与头颈鳞状细胞癌 (HNSCC) 的较高复发率相关。硼替佐米（一种通过抑制蛋白酶体的 NF-κ B 抑制剂）与多西他赛联合使用的疗效和毒性进行了评估。 材料和方法：患有复发性和/或转移性 HNSCC 的患者被纳入 II 期硼替佐米/多西他赛试验（硼替佐米 1.6 mg/m(2) 和多西他赛 40 mg/m(2)，在试验的第 1 天和第 8 天）。 21天为一个周期）。使用 RECIST 评估疗效。评估组织样本中是否存在人乳头瘤病毒 (HPV) 和 NF-κ B 相关基因的表达。 结果：25 名入组患者中，有 21 名可评估缓解； 1 例部分缓解（PR，5%），10 例疾病稳定（SD，48%）和 10 例疾病进展（PD，48%）。与 PD 患者相比，PR/SD 患者的生存期明显更长，并且该方案耐受性良好。 20 个肿瘤中只有 1 个呈 HPV 阳性。通过基因表达分析，PD患者的肿瘤中NF-κB和表皮生长因子受体相关基因的表达较高。结论：进一步了解硼替佐米和多西他赛之间的治疗耐药性和相互作用可能为治疗HNSCC提供新的方法。
Background: Our previous study has shown that nuclear factor-kappa B (NF-kappa B)-signaling pathway was associated with a higher rate of recurrence in head and neck squamous cell carcinoma (HNSCC). The combination of bortezomib, an NF-kappa B inhibitor by inhibition of proteasomes, plus docetaxel was assessed for efficacy and toxicity.Materials and methods: Patients with recurrent and/or metastatic HNSCC were enrolled on a phase II bortezomib/docetaxel trial (bortezomib 1.6 mg/m(2) and docetaxel 40 mg/m(2) on days 1 and 8 of a 21-day cycle). Response was assessed using RECIST. Tissue specimens were evaluated for the presence of human papillomavirus (HPV) and expression of NF-kappa B-associated genes.Results: Twenty-one of 25 enrolled patients were assessable for response; one partial response (PR, 5%), 10 stable disease (SD, 48%) and 10 progressive disease (PD, 48%). Patients with PR/SD had significantly longer survival compared with patients with PD and the regimen was well tolerated. Only one of 20 tumors was positive for HPV. Patients with PD had higher expression of NF-kappa B and epidermal growth factor receptor-associated genes in their tumors by gene expression analysis.Conclusion: Further understanding of treatment resistance and interactions between bortezomib and docetaxel may provide novel approaches in managing HNSCC.