A phase II study of 5-fluorouracil and high dose folinic acid in cisplatin refractory metastatic bladder cancer
A phase II study of 5-fluorouracil and high dose folinic acid in cisplatin refractory metastatic bladder cancer
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DOI：
10.1093/oxfordjournals.annonc.a059325
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发表时间：
1995-10-01
影响因子：
50.5
通讯作者：
Stewart, DJ
中科院分区：
文献类型：
--
作者：
Huan, SD;Aitken, SE;Stewart, DJ
背景：膀胱癌是一种化疗敏感性肿瘤，然而，对于先前以顺铂为基础的化疗后治疗无效或复发的转移性疾病患者，尚无有效的治疗方法。单药 5-氟尿嘧啶对膀胱癌具有适度的活性。 5-氟尿嘧啶与亚叶酸的组合导致5-氟脱氧尿苷单磷酸-胸苷酸合成酶-5,10亚甲基四氢叶酸的三元复合物稳定，导致DNA抑制增加和5-氟尿嘧啶的细胞毒性增加。 患者和方法：14名可评估的转移性膀胱癌患者接受300 mg/m(2)的5-氟尿嘧啶和200 mg/m(2)的亚叶酸治疗。每天 200 mg/m(2)，持续五天。结果：没有完全或部分反应。一名患者反应轻微，三名患者病情稳定。 25%的患者出现腹泻和粘膜炎。发生1例治疗相关死亡。结论：高剂量亚叶酸并没有增加5-氟尿嘧啶对顺铂失败后转移性膀胱癌的细胞毒性。
Background: Bladder cancer is a chemosensitive tumour, however, there is no effective therapy for patients with metastatic disease who failed to respond or relapsed after prior treatment with cisplatin-based chemotherapy. Single agent 5-fluorouracil has modest activity in bladder cancer. The combination of 5-fluorouracil with folinic acid results in stabilization of the ternary complex of 5-fluorodeoxyuridine monophosphate-thymidylate synthetase-5,10 methylene tetrahydrofolate leading to increased DNA inhibition and increased cytotoxicity of 5-fluorouracil.Patients and methods: Fourteen evaluable patients with metastatic bladder cancer were treated with 5-fluorouracil at 300 mg/m(2) and folinic acid at 200 mg/m(2) daily for five days.Results: There were no complete or partial responses. One patient had a minor response and three patients had stable disease. Diarrhea and mucositis occurred in 25% of patients. There was one treatment-related death.Conclusion: High dose folinic acid did not increase the cytotoxicity of 5-fluorouracil in metastatic bladder cancer after cisplatin failure.