PHASE-II STUDY OF COUMARIN AND CIMETIDINE IN PATIENTS WITH METASTATIC RENAL-CELL CARCINOMA
PHASE-II STUDY OF COUMARIN AND CIMETIDINE IN PATIENTS WITH METASTATIC RENAL-CELL CARCINOMA
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DOI：
10.1200/jco.1990.8.2.325
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发表时间：
1990-02-01
影响因子：
45.3
通讯作者：
DOZIER, N
中科院分区：
文献类型：
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作者：
DEXEUS, FH;LOGOTHETIS, CJ;DOZIER, N
50例局部晚期或转移性肾癌患者从第1天开始口服香豆素(1，2-苯并吡喃酮)100 mg，从第15天开始口服西咪替丁300 mg，每天4次。随着病情进展，香豆素增加到每天100 mg，每天4次。3名患者(6%；95%可信区间[CI]，2%至17%)获得部分缓解，其中一名患者在剂量递增后。此外，1名患者有轻微反应，然后病情进展，并在剂量增加后再次出现轻微反应。所有四名应答者都有不可评估的原发肿瘤(三名曾接受过肾切除术，一名曾患肾血管梗塞)。唯一的主要毒性是肾脏(37名患者血清肌酐水平轻度至中度升高)。治疗前后进行的免疫学检查(超敏皮肤试验、淋巴细胞转化反应、淋巴细胞数量、T淋巴细胞、T辅助细胞和T抑制细胞亚群、T辅助细胞和T抑制细胞亚群，以及T辅助细胞和抑制T细胞的比率)显示，在基线水平，淋巴细胞相对减少，超敏皮肤试验结果降低，T细胞和T辅助细胞和T抑制细胞亚群的数量随着时间的推移而普遍下降。在测试的任何免疫学参数中都没有增强。应答率为6%，低于先前报道的；基线时注意到全身免疫缺陷，淋巴细胞减少随着疾病的进展而恶化，未受影响的治疗。
Fifty patients with locally advanced or metastatic renal cell carcinoma were treated with coumarin (1,2-benzopyrone) at 100 mg orally daily starting on day 1 and cimetidine 300 mg orally four times a days starting on day 15. When disease progressed, coumarin was escalated to 100 mg orally four times a day. Three patients (6%; 95% confidence interval [CI], 2% to 17%) achieved a partial response, one of those after dose escalation. In addition, one patient had a minor responses, then progressing disease, and again had a minor response after dose escalation. All four responders had nonassessable primary tumors (three had had prior nephrectomy and one a renal angioinfarction). The only major toxicity was renal (37 patients had minor to moderate elevations in serum creatinine level). Immunologic studies (hypersensitivity skin testing, lymphocyte blastogenesis response, number of lymphocytes, T lymphocytes, T helper and T suppressor subsets, and T helper:suppressor ratio), performed before and after therapy, showed a relative lymphopenia and decreased hypersensitivity skin-testing results at baseline, and a general decline over time in the number of T cells and T helper and T suppressor subsets. There was no enhancement in any of the immunologic parameters tested. The response rate was 6%, lower than previously reported; a general immunodeficiency was noted at baseline, and the lymphopenia worsened with progressing disease, unaffected therapy.