Phase II trial of the histone deacetylase inhibitor vorinostat (Zolinzaâ„¢, suberoylanilide hydroxamic acid, SAHA) in patients with recurrent and/or metastatic head and neck cancer
Phase II trial of the histone deacetylase inhibitor vorinostat (Zolinzaâ„¢, suberoylanilide hydroxamic acid, SAHA) in patients with recurrent and/or metastatic head and neck cancer
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DOI：
10.1007/s10637-007-9075-2
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发表时间：
2008-02-01
影响因子：
3.4
通讯作者：
Frankel, Stanley R.
中科院分区：
文献类型：
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作者：
Blumenschein, George R., Jr.;Kies, Merrill S.;Frankel, Stanley R.
该II期试验开始评估口服伏立诺他（Zolinza（TM），辛二酰苯胺异羟肟酸，SAHA）在复发性和/或转移性头颈癌患者中的疗效和安全性。符合条件的患者必须患有对常规化疗无反应或不耐受的复发性和/或转移性头颈癌。患者必须有可测量的疾病、足够的血液学、肝脏和肾脏功能，并且能够吞下胶囊。自既往化疗、放疗、大手术或研究性抗癌治疗以来必须已过去4周或更长时间，并且患者必须已从既往毒性中恢复。研究终点包括缓解率、疾病稳定持续时间和无进展生存期。13例患者入组（9例男性）; 1例在开始治疗前撤回知情同意书。12例患者接受口服伏立诺他400 mg每日一次，可评价反应。中位年龄为54岁（范围40-82岁）。所有患者既往均接受过化疗（包括10例铂类或紫杉烷类联合治疗），9例既往接受过放疗。未观察到确认的部分或完全缓解。观察到1例未证实的部分缓解。3例患者病情稳定，范围为9至26周。9例患者因疾病进展而停药，2例患者撤回知情同意书，1例患者因3级厌食而停药。3-4级药物相关毒性包括血小板减少症（n=3）、厌食症（n=2）和脱水（n=2）。口服伏立诺他400 mg qd通常耐受性良好，但在这一小组接受过大量预治疗的患者中未显示出根据肿瘤缓解定义的疗效。
This phase II trial was initiated to assess the efficacy and safety of oral vorinostat (Zolinza(TM), suberoylanilide hydroxamic acid, SAHA) in patients with recurrent and/or metastatic head and neck cancer. Eligible patients must have recurrent and/or metastatic head and neck cancer unresponsive to or intolerant of conventional chemotherapy. Patients must have measurable disease, adequate hematologic, hepatic, and renal function, and be able to swallow capsules. Four or more weeks must have elapsed since prior chemotherapy, radiation therapy, major surgery or investigational anticancer therapy, and patients must have recovered from prior toxicities. Study endpoints included response rate, duration of stable disease and progression-free survival. Thirteen patients were enrolled (9 males); 1 withdrew consent prior to starting therapy. Twelve patients received oral vorinostat 400 mg once daily and were evaluable for response. The median age was 54 years (range 40-82). All patients had received prior chemotherapy (including 10 with platinum- or taxane-based combination therapy), and 9 had prior radiation therapy. No confirmed partial or complete responses were observed. One unconfirmed partial response was seen. Three patients had stable disease ranging from 9 to 26 weeks. Nine patients discontinued due to progressive disease, two withdrew consent, and one discontinued therapy for grade 3 anorexia. Grades 3-4 drug-related toxicities included thrombocytopenia (n=3), anorexia (n=2), and dehydration (n=2). Oral vorinostat 400 mg qd was generally well tolerated but did not demonstrate efficacy as defined by tumor response in this small group of heavily pre-treated patients.