氟尿苷用于滋养细胞肿瘤治疗的临床药效学研究

Studies on the pharmacodynamics of floxuridine in patients with trophoblastic neoplasms

目的 评价氟尿苷 (FUDR)用于滋养细胞肿瘤化疗时的临床疗效和不良反应并与氟尿嘧啶 (5FU)进行对比。方法 19名患者入选并被分入单药化疗组或联合化疗组。根据自身对照的原则 ,单药化疗组的 9名患者先后给予 5FU或FUDR ,联合化疗组的 10名患者先后给予FUDR +KSM或 5FU +KSM。记录化疗前后 β HCG水平 ,白细胞、中性粒细胞和血小板水平 ,消化道不良反应等 ,计算药物对肿瘤细胞的杀灭率 =log(β HCG化疗前/ β HCG化疗后)。结果 ①单药化疗FUDR组的肿瘤细胞杀灭率为 (1.4 7± 0 .86 ) ,5FU组为 (1.6 5± 0 .90 ) ,均有较好的疗效 (P =0 .6 815 )。②联合化疗时FUDR组的肿瘤细胞杀灭率为 (1.38± 0 .71) ,5FU组为 (1.4 0± 0 .91) ,无显著差异 (P =0 .96 78)。③FUDR单药化疗组与联合化疗组的疗效相比 ,差异不明显 (P =0 .84 2 1) ,5FU的单药化疗与联合化疗之间亦无差异 (P =0 .5 5 5 8)。④从不同疗程与肿瘤细胞杀灭率的关系看 ,单药化疗时 5FU组与FUDR组差异不大 ;而联合化疗时FUDR组的疗效恒定 (P =0 .990 3) ,而 5FU组的耐药性较为明显 (P =0 .0 2 6 6 )。⑤单药化疗时FUDR的血液毒性要显著强于 5FU ,而联合化疗时FUDR组与 5FU组的血液毒性相当。⑥ 5FU组严重消化道不良反应的发生率要明显高于FUDR?

OBJECTIVE: To evaluate the efficacy and adverse effects of floxuridine in the treatment of patients with trophoblastic neoplasms, and to compare that of floxuridine with 5FU. METHODS: 19 patients were enrolled and divided into single drug chemotherapy (FUDR/5FU) group or combination chemotherapy (FUDR + KSM/5FU + KSM) group. With the cross-over self-control way, 9 patients in the single drug chemotherapy group were intravenously infused FUDR or 5FU for 8 hr, respectively. 10 patients in the combination chemotherapy (FUDR + KSM/5FU + KSM) group were administered FUDR + KSM or 5FU + KSM as intravenous infusion for 8 hr. β-HCG level, WBC, neutrocyte, platelets counts before and after chemotherapy were recorded respectively. Nausea, vomiting and liver function were recorded as the adverse effects. The efficacy of chemotherapy was estimated as log(β-HCGbefore chemotherapy/β-HCGafter chemotherapy). RESULT: The same value of log(β-HCGbefore chemotherapy/β-HCGafter chemotherapy) in patients administered FUDR or FUDR + KSM was obtained as that of patients administered 5FU or 5FU + KSM. The incidence of hematological toxicity of FUDR was greater than that of 5FU, and the gastrointestinal adverse event following 5FU intravenous infusion were much more than that of FUDR. The correlation between the pharmacokinetics and pharmacodynamics of FUDR was not found yet. CONCLUSION: FUDR showed the same efficacy and safety as that of 5FU in the treatment of patients with trophoblastic neoplasms. It may also be used in substitute of 5FU in single drug or multiple-drugs chemotherapy.