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（1）與5-氟尿嘧啶（5-FU）合用提高5-FU的療效
在DNA合成過(guò)程中dUMP需要在胸苷酸合成酶（TMPS）的作用下接受四氫葉酸的 甲基形成dTMP。而5-FU進(jìn)入體內(nèi)先轉(zhuǎn)變?yōu)榉蜞奏っ撗鹾塑账�，抑制胸苷酸合成酶的作用。在反�?yīng)過(guò)程中，TMPS、四氫葉酸和dUMP三者形成一個(gè)過(guò)渡性的復(fù)合物，反應(yīng)結(jié)束后復(fù)合物分解，釋放出二氫葉酸、TMPS和dTMP。但給予5-FU后形成的三聯(lián)復(fù)合物不能分解，TMPS的功能受到抑制，不能生成dTMP。氟尿嘧啶脫氧核苷酸與酶的結(jié)合力與四氫葉酸的濃度成正比，提高四氫葉酸的濃度可加強(qiáng)5-FU對(duì)TMPS的抑制作用。
臨床上，5-FU與CF的合用常見(jiàn)于各種消化道的惡性腫瘤，如胃癌、大腸癌等。有作者研究發(fā)現(xiàn)，在晚期大腸癌患者中，單用5-FU與5-FU、CF合用的有效率存在顯著性差異（11%和23%，P<0.001）。但CF與5-FU合用時(shí)的劑量卻一直存在爭(zhēng)議，多數(shù)隨機(jī)對(duì)照研究提示低劑量（20mg/m2）與高劑量（200-500mg/m2）相比療效上無(wú)顯著性差異。
（2）大劑量氨甲蝶呤（MTX）的解救治療
氨甲蝶呤與葉酸的結(jié)構(gòu)相似，并與二氫葉酸還原酶具有較高的親和力，它可在細(xì)胞內(nèi)競(jìng)爭(zhēng)性地與二氫葉酸還原酶相結(jié)合，阻斷二氫葉酸轉(zhuǎn)變?yōu)樗臍淙~酸，從而抑制DNA的合成。CF進(jìn)入體內(nèi)后，通過(guò)四氫葉酸還原酶轉(zhuǎn)變?yōu)樗臍淙~酸，從而有效的拮抗MTX的作用。因此外源性的給予CF可以越過(guò)MTX所作用的部位，使正常的生化反應(yīng)能夠繼續(xù)進(jìn)行起到解救作用。
所謂大劑量MTX是指每次的劑量比常規(guī)劑量大100倍以上（一般為2-5g/m2），一般靜脈輸注4-6小時(shí)，使一段時(shí)間內(nèi)血中藥物濃度達(dá)到較高水平，促使MTX進(jìn)入細(xì)胞內(nèi)的濃度達(dá)到10-5 M以上的有效濃度。另一方面，血藥濃度提高后，還可使MTX擴(kuò)散到血供較差的實(shí)體瘤中，并能通過(guò)血腦、血眼和血睪屏障。因此，大劑量MTX與常規(guī)劑量相比療效更好。
但是大劑量MTX治療也可以引起嚴(yán)重的不良反應(yīng)，如骨髓抑制、嚴(yán)重的黏膜炎、腎功能衰竭、消化道反應(yīng)、肝功能損害等。因此，MTX治療后一段時(shí)間必須采取解救措施。
�。�3）藥代動(dòng)力學(xué)
CF口服后幾乎可被全部吸收，在肝臟及腸黏膜被代謝�？赏ㄟ^(guò)血腦屏障。靜脈或肌肉注射后半衰期為6小時(shí)。80-90%的藥物經(jīng)腎臟排泄，5-8%的藥物經(jīng)糞便排泄。
3.不良反應(yīng)
極少發(fā)生過(guò)敏反應(yīng)。大劑量應(yīng)用后可出現(xiàn)胃腸功能紊亂、失眠、抑郁或煩躁.
4.用法用量
（1）與5-FU合用時(shí)的最合適劑量目前尚不清楚，常規(guī)的方法是200-500mg/m2，在5-FU之前靜脈輸注2小時(shí)，隨后靜脈應(yīng)用5-FU，一般連用5天，21-28天重復(fù)治療。
�。�2）用于大劑量MTX的解救治療。
可采用肌肉注射、靜脈注射、靜脈輸注和口服等方法。因?yàn)镃F幾乎可以被完全吸收，因此不同的用藥途徑對(duì)CF的作用影響不大。CF解救一般在大劑量MTX治療后2-18小時(shí)（最晚不超過(guò)24小時(shí)）開(kāi)始，劑量為6-12mg/m2，隨后每隔3-6小時(shí)重復(fù)同樣劑量給藥，一般解救應(yīng)持續(xù)到72小時(shí)以上或血中MTX的濃度降到10-7M的安全值以下。如果MTX的毒性較大或血藥濃度較高時(shí)，CF的解救時(shí)間應(yīng)適當(dāng)延長(zhǎng)至5-7天，劑量也應(yīng)加大。
CF解救治療的同時(shí)，還要水化、堿化尿液、并給予一定的支持治療。
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