Milano G, Renée N
Centre Antoine-Lacassagne, Nice, France.
Bull Cancer. 1995 Mar;82(3):189-95.
The potentiation of 5-fluorouracil (5FU) cytotoxicity by folinic acid (FA) is based on strong experimental basis. This experimental concept has been prolonged in the clinical setting where 5FU-FA combination has demonstrated its superiority in comparison to 5FU alone for the chemotherapeutic treatment of advanced colorectal cancer. A justified question concerns the stability for 5FU (new French preparation, with sodium hydroxyde, by Roche)-FA admixtures studied in clinically compatible conditions. We have presently undertaken this study. Based on drug concentrations corresponding to current 5FU-FA chemotherapeutic protocols, we have tested the influence of various factors like the vials, diluents and the type of FA preparation (Lederfoline versus Elvorine). The mixture between 5FU and FA leads to the formation of a precipitate which is influenced by the contact time between 5FU and FA (threshold at 24 hr), by the relative concentration of each drug in mixture and its seems necessary to avoid the mixture between undiluted 5FU and FA (d,1 preparation, Lederfoline). Cassettes or plastic bags are preferable to glass recipients. Finally and above all, the use of pure lFA form (Elvorine) does not lead to the formation of a precipitate seen with the d'1 FA form (Lederfoline) at equal concentration of active folate (1 form). These data carry practical importance for the security and the quality of 5FU-FA protocols and particularly when using portable pumps during prolonged periods necessitating the use of small volume of injectable drug solutions.
亚叶酸(FA)增强5-氟尿嘧啶(5FU)细胞毒性有坚实的实验基础。这一实验概念已延伸至临床领域,在晚期结直肠癌的化疗中,5FU与FA联合用药已证明其相对于单独使用5FU的优越性。一个合理的问题涉及在临床适用条件下研究的5FU(罗氏公司新的含氢氧化钠的法国制剂)-FA混合液的稳定性。我们目前开展了这项研究。基于当前5FU-FA化疗方案对应的药物浓度,我们测试了各种因素的影响,如小瓶、稀释剂以及FA制剂类型(亚叶酸钙与亚叶酸)。5FU与FA混合会形成沉淀,沉淀受5FU与FA接触时间(24小时为阈值)、混合液中每种药物的相对浓度影响,似乎有必要避免未稀释的5FU与FA混合(d,1制剂,亚叶酸钙)。使用盒式容器或塑料袋优于玻璃容器。最后且最重要的是,在活性叶酸浓度相等(1种形式)时,使用纯lFA形式(亚叶酸)不会像d'1 FA形式(亚叶酸钙)那样形成沉淀。这些数据对5FU-FA方案的安全性和质量具有实际重要性,尤其是在长时间使用便携式泵且需要使用小体积注射用药物溶液时。