Infusions of fluorouracil and leucovorin: Effects of the timing and semi-intermittency of drug delivery
Infusions of fluorouracil and leucovorin: Effects of the timing and semi-intermittency of drug delivery
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DOI：
10.1159/000012031
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发表时间：
1999-01-01
期刊：
影响因子：
3.5
通讯作者：
Conte, P
中科院分区：
文献类型：
--
作者：
Falcone, A;Allegrini, G;Conte, P
临床前和临床研究已经证明，5-FU递送的昼夜节律调节可以降低毒性并提高抗肿瘤活性。然而，5-FU给药时机的相对重要性尚未在临床上得到解决。本研究的目的是确定5-氟尿嘧啶（5-FU）和甲酰四氢叶酸（LV）方案的毒性，最大耐受剂量和活性，该方案根据平坦或三种不同的时间调节节律连续输注14天。共有113名患者进入研究，四组患者的特征相似。毒性主要包括口腔炎和腹泻，并且在允许递送更高剂量强度的所有三个时间组中观察到毒性降低。四组之间的应答率没有显著差异。这些结果表明，通过非正弦昼夜节律调节输注可降低5-FU+LV毒性并增加5-FU剂量强度。然而，观察到的毒性降低似乎主要取决于准耐受性，而不是5-FU+LV给药的时间。
Preclinical and clinical studies have demonstrated that the circadian modulation of 5-FU delivery may reduce toxicities and improve antitumor activity. However, the relative importance of the timing of 5-FU delivery has not been clinically addressed. The aims of this study were to determine the toxicities, the maximum tolerable doses and the activity of a regimen with 5-fluorouracil (5-FU) and leucovorin (LV) administered as a 14-day continuous infusion according to a flat or three different chronomodulated rhythms in patients with metastatic gastrointestinal carcinomas. A total of 113 patients entered the study and their characteristics were comparable among the four groups. Toxicities included mainly stomatitis and diarrhea, and a reduced toxicity was observed in all the three chronogroups that allowed the delivery of higher dose intensities. Response rates were not significantly different among the four groups. These results suggest that a reduction in 5-FU+LV toxicity and an increase in 5-FU dose intensity can be obtained by a nonsinusoidally circadian modulated infusion. However, the reduction in toxicity observed seems to be dependent mainly on the quasi-intermittency and not on the timing of 5-FU+LV delivery.