PHASE-II STUDY OF THE ANTIFOLATE N-10-PROPARGYL-5,8-DIDEAZAFOLIC ACID (CB-3717) IN ADVANCED BREAST-CANCER
PHASE-II STUDY OF THE ANTIFOLATE N-10-PROPARGYL-5,8-DIDEAZAFOLIC ACID (CB-3717) IN ADVANCED BREAST-CANCER
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DOI：
10.1016/0277-5379(88)90307-0
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发表时间：
1988-04-01
期刊：
影响因子：
--
通讯作者：
CALVERT, AH
中科院分区：
文献类型：
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作者：
CANTWELL, BMJ;MACAULAY, V;CALVERT, AH
52例进行性晚期乳腺癌患者接受了新型叶酸拮抗剂CB 3717（N10-炔丙基-5，8-二去氮叶酸）的治疗，该药物可抑制胸苷酸合成酶。46名患者接受了激素预治疗，43名患者接受了细胞毒性化疗，39名患者接受了两种治疗。CB 3717给药后，48例可评价缓解的患者中有8例（16.6%）出现部分缓解（置信限7.4- 30.2%，95%置信水平）。肝功能异常（大多数情况下可逆）是最常见的毒性，通常伴有不适。8例患者发生重度肾衰竭，其中5例对CB 3717有部分反应。这项研究显示了胸苷酸合成酶作为治疗靶点的重要性，但CB 3717的临床价值受到其肝脏和肾脏毒性的限制。
Fifty-two patients with progressive advanced breast cancer were treated with the novel antifolate CB 3717 (N10-propargyl-5,8-dideazofolic acid) which inhibits thymidylate synthetase. Forty-six patients were pretreated with hormones, 43 with cytotoxic chemotherapy and 39 patients with both treatments. Eight of 48 patients (16.6%) evaluable for response had partial responses (confidence limits 7.4-30.2%, 95% confidence level) following CB 3717 administration. Liver function abnormalities, reversible in most cases, were the commonest toxicities and were frequently accompanied by malaise. Severe renal failure occurred in eight patients, five of whom had had partial responses to CB 3717. This study shows the importance of thymidylate synthetase as a target for therapy but the clinical value of CB 3717 is limited by its hepatic and renal toxicities.