A phase II study of sunitinib in recurrent and/or metastatic adenoid cystic carcinoma (ACC) of the salivary glands: current progress and challenges in evaluating molecularly targeted agents in ACC
A phase II study of sunitinib in recurrent and/or metastatic adenoid cystic carcinoma (ACC) of the salivary glands: current progress and challenges in evaluating molecularly targeted agents in ACC
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DOI：
10.1093/annonc/mdr522
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发表时间：
2012-06-01
影响因子：
50.5
通讯作者：
Siu, L. L.
中科院分区：
文献类型：
--
作者：
Chau, N. G.;Hotte, S. J.;Siu, L. L.
背景：血管内皮生长因子（VEGF）和c-kit在腺样囊性癌（ACC）中高表达，并与生物侵袭性相关。本研究旨在评估舒尼替尼在唾液腺ACC中的抗肿瘤活性，舒尼替尼是一种血管内皮生长因子受体、c-kit、血小板衍生生长因子受体、ret原癌基因（ret）和fms样酪氨酸激酶3 （FLT3）的多靶点抑制剂。患者和方法：在这项单组、两期的II期试验中，进展性、复发性和/或转移性ACC患者每天接受37.5 mg舒尼替尼治疗。每8周评估一次疗效。结果：14例患者入组研究。在13例可评估的患者中，无客观反应，11例患者病情稳定（SD）， 8例患者病情稳定（SD = 6个月），2例患者病情进展为最佳反应。中位进展时间为7.2个月。中位总生存期为18.7个月。至少50%的患者出现的毒性作用包括疲劳、口腔黏膜炎和低磷血症，通常为轻至中度严重程度。结论：虽然没有观察到反应，但舒尼替尼耐受性良好，在62%的可评估患者中，肿瘤稳定时间延长了6个月。缺乏反应与其他针对ACC的分子靶向药物的试验相当，这突出了在II期临床试验设计中需要新的策略。
Background: Vascular endothelial growth factor (VEGF) and c-kit are highly expressed in adenoid cystic carcinoma (ACC) and associated with biologic aggressiveness. This study aimed to assess the antitumor activity of sunitinib, a multi-targeted inhibitor of vascular endothelial growth factor receptor, c-kit, platelet-derived growth factor receptor, ret proto-oncogene (RET) and FMS-like tyrosine kinase 3 (FLT3), in ACC of the salivary gland.Patients and methods: Patients with progressive, recurrent and/or metastatic ACC were treated with sunitinib 37.5 mg daily in this single-arm, two-stage phase II trial. Response was assessed every 8 weeks.Results: Fourteen patients were enrolled on to the study. Among 13 assessable patients, there were no objective responses, 11 patients had stable disease (SD), 8 patients had SD >= 6 months and 2 patients had progressive disease as best response. Median time to progression was 7.2 months. Median overall survival was 18.7 months. Toxic effects occurring in at least 50% of patients included fatigue, oral mucositis and hypophosphatemia usually of mild to moderate severity.Conclusions: Although no responses were observed, sunitinib was well tolerated, with prolonged tumor stabilization of >= 6 months in 62% of assessable patients. The lack of responses is comparable with other trials of molecularly targeted agents in ACC and highlights the need for novel strategies in phase II clinical trial design.