Evaluation of the combination of vinblastine and quinidine in patients with metastatic renal cell carcinoma. A phase I study.
Evaluation of the combination of vinblastine and quinidine in patients with metastatic renal cell carcinoma. A phase I study.
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长春花碱和奎尼丁联合治疗转移性肾细胞癌的评价。
DOI：
10.1097/00000421-199506000-00006
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Ernstoff,MS
中科院分区：
文献类型：
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作者：
Agarwala,SS;Bahnson,RR;Wilson,JW;Szumowski,J;Ernstoff,MS
已知奎尼丁可抑制 p-糖蛋白并增强长春花碱对抗培养的肾癌细胞的活性。我们在转移性肾细胞癌患者的 I 期试验中联合使用了奎尼丁和长春花碱。共有二十三名患者入组。既往治疗包括肾切除术（15 名患者）、放射治疗（1 名患者）和干扰素（8 名患者）。患者队列接受三种奎尼丁剂量水平之一（100、200 和 400 mg）的治疗；一名患者接受了 300 毫克的治疗。在每周一次静脉内给予第一剂长春花碱5 mg/m 2 之前3天开始，每日口服奎尼丁4次。每周监测血液学参数、心电图和奎尼丁水平。每个剂量层的平均奎尼丁水平分别为 1.58、2.59 和 4.24 μg/ml。剂量限制性毒性是白细胞减少症，16 名患者因此需要中断剂量。每个剂量层的平均最低白细胞计数 (× 10 9/L) 分别为 3.47、2.3 和 1.73。白细胞计数相对于基线的平均最大下降的相应值分别为 3.85、5.86 和 6.53。随着奎尼丁剂量的增加，白细胞减少症有变得更加严重的趋势。其他毒性包括所有患者均出现轻度恶心和呕吐，各一名患者出现低血压和麻痹性肠梗阻。没有观察到心脏毒性。 1 名患者完全缓解，4 名患者病情稳定。我们的结论是，奎尼丁和长春花碱可以在临床环境中安全地一起给药，白细胞减少症是剂量限制的。需要进一步的研究来确定相对于单独使用长春花碱的任何治疗优势。
Quinidine is known to inhibit p-glycoprotein and enhance the activity of vinblastine against cultured renal carcinoma cells. We have combined quinidine and vinblastine in a Phase I trial in patients with metastatic renal cell carcinoma. Twenty-three patients were entered. Prior treatment included nephrectomy (15 patients), radiation (1 patient) and interferons (8 patients). Cohorts of patients were treated at one of three quinidine dose levels (100. 200, and 400 mg); one patient received 300 mg. Quinidine was given orally 4 times daily starting 3 days prior to the first dose of vinblastine of 5 mg/m 2 intravenously given once a week. Hematologic parameters, EKG, and quinidine levels were monitored weekly. Mean quinidine levels in each dose tier were 1.58, 2.59, and 4.24 μg/ml, respectively. The dose-limiting toxicity was leukopenia, which necessitated dose interruptions in 16 patients. The mean nadir WBC count (× 10 9/L) was 3.47, 2.3, and 1.73 in each dose tier, respectively. Corresponding values for the mean maximum decrease in WBC count from baseline were 3.85, 5.86, and 6.53, respectively. There was a trend for leukopenia to become more severe with increasing doses of quinidine. Other toxicities included mild nausea and vomiting in all patients, and hypotension and paralytic ileus in one patient each. No cardiac toxicity was observed. One patient had a complete remission and 4 patients had stable disease. We conclude that quinidine and vinblastine may be administered together safely in a clinical setting, with leukopenia being dose-limiting. Further studies are needed to determine any therapeutic advantage over vinblastine alone.