Phase I trial of N-methylformamide.
Phase I trial of N-methylformamide.
复制标题
N-甲基甲酰胺的I期试验。
DOI：
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发表时间：
1984
期刊：
影响因子：
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通讯作者：
R. Dubbelman
中科院分区：
文献类型：
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作者：
J. Mcvie;W. W. ten Bokkel Huinink;G. Simonetti;R. Dubbelman
在一项 I 期研究中，N-甲基甲酰胺先静脉注射，随后口服给 19 名患者，起始剂量为 300 mg/m2/天 X 5。计划每 2 周重复一次周期，剂量分四步递增至 1200 mg/m2/天 X 5。该药物的主要毒性作用是恶心和呕吐，但这还不足以干扰口服药物。平行的生物利用度研究证实了该药物的良好吸收。生化紊乱包括与剂量无关的转氨酶可逆性升高、一名患者的周围神经病变以及另一名患者的药物与酒精的相互作用。剂量限制性毒性作用是可逆性高胆红素血症。一名患者出现黄疸。在 15 名可评估的患者中，有两名部分缓解（前列腺癌和宫颈癌）和两名最小缓解（卵巢癌和肾上腺瘤）。 II 期研究的推荐剂量为 800 mg/m2/天 X 5 次口服，每 2 或 3 周重复一次。
N-methylformamide was administered iv and later orally to 19 patients in a phase I study, with a starting dose of 300 mg/m2/day X 5. The cycles were planned to be repeated every 2 weeks, and doses were escalated in four steps to 1200 mg/m2/day X 5. The principal toxic effect of the drug was nausea and vomiting, but this was not severe enough to interfere with oral medication. Parallel bioavailability studies confirmed excellent absorption of the drug. Biochemical disturbances included reversible elevation in transaminases not related to dose, peripheral neuropathy in one patient, and drug interaction with alcohol in another. The dose-limiting toxic effect was reversible hyperbilirubinemia. One patient became jaundiced. Among 15 evaluable patients, there were two partial responses (prostate and cervix carcinoma) and two minimal responses (ovarian carcinoma and hypernephroma). The recommended dose for the phase II study is 800 mg/m2/day X 5 orally, repeated every 2 or 3 weeks.