A phase II trial of 17-(Allylamino)-17-demethoxygeldanamycin in patients with papillary and clear cell renal cell carcinoma
A phase II trial of 17-(Allylamino)-17-demethoxygeldanamycin in patients with papillary and clear cell renal cell carcinoma
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DOI：
10.1007/s10637-006-9208-z
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发表时间：
2006-11-01
影响因子：
3.4
通讯作者：
Motzer, Robert J.
中科院分区：
文献类型：
--
作者：
Ronnen, Ellen A.;Kondagunta, G. Varuni;Motzer, Robert J.
本研究的目的是检测热休克蛋白90(HSP90)抑制剂17-(烯丙氨基)-17-去甲氧基吉达那霉素(17-AAG)对转移性乳头状肾细胞癌(RCC)和转移性透明细胞癌(RCC)患者的抗肿瘤活性。符合条件的患者根据组织学亚型分为2组：乳头状型或透明细胞型。所有患者均患有晚期肾细胞癌并伴有可测量的疾病，卡诺夫斯基评分至少为70分，且无脑转移的证据。在这项II期试验中，12例透明细胞肾癌和8例乳头状肾癌患者接受了17-AAG治疗。17-AAG以220 mg/m(2)的速度静脉滴注，每周2次，连续2周，然后休息1周。周期为21天。两组患者均无完全或部分缓解。毒副作用包括肝功能升高、视神经炎、呼吸困难、疲劳和胃肠道副作用。20名患者中有6名需要减少剂量。在这项试验中使用的剂量和方案下，17-AAG在治疗透明细胞或乳头状肾细胞癌患者方面没有取得客观反应。
The aim of this study was to determine the antitumor activity of 17-(Allylamino)-17-demethoxyge-ldanamycin (17-AAG), a heat shock protein 90(hsp90) inhibitor in patients with metastatic papillary renal cell carcinoma (RCC) or metastatic clear cell RCC. Eligible patients were divided into 2 cohorts based on histological subtype: papillary or clear cell RCC. All patients had advanced RCC with measurable disease, a Karnofsky performance status of at least 70, and no evidence of brain metastases. Twelve patients with clear cell RCC and 8 patients with papillary RCC were treated with 17-AAG on this phase II trial. 17-AAG was given intravenously at 220 mg/m(2) twice weekly for 2 weeks followed by a week of rest. Cycle length was 21 days. No patient in either cohort achieved a complete or partial response. Toxicities included elevated liver function tests, optic neuritis, dyspnea, fatigue, and gastrointestinal side effects. Six of the 20 patients required dose reduction. At the dose and schedule used in this trial, 17-AAG did not achieve objective response in the treatment of clear cell or papillary renal cell carcinoma patients.