Carmofur-induced leukoencephalopathy: MRI

Carmofur, a derivative of 5-fluorouracil, has recently been noted to have an infrequent but serious association with leukoencephalopathy. To our knowledge, there has been no report of early MRI findings in this leukoencephalopathy. We describe a case in which diffuse high signal intensity of the entire cerebral white matter, including the corpus callosum, was seen on T2-weighted magnetic resonance images. Although similar findings can be seen in many other diseases, carmofur-induced leukoencephalopathy should be suspected in a patient treated with carmofur. It is important to know the clinical and MRI characteristics of this condition, for early diagnosis and better prognosis.     

HPLC法测定卡莫氟片的含量及溶出度

目的：采用高效液相色谱法测定卡莫氟片的含量和溶出度。方法：以十八烷基硅烷键合硅胶为填充剂,以甲醇-0．25％醋酸溶液为流动相,检测波长为258nm。结果：卡莫氟在0．00768～0．06912g·L^-1浓度范围内线性关系良好,平均回收率为100．06％,RSD=0．82％（n=9）。结论：方法简便、快速、结果准确。     

SUBACUTE NEUROTOXICITY OF 5-FLUOROURACIL and ITS DERIVATIVE, CARMOFUR, IN CATS

The subacute neurotoxicity of 5-fluorouracil (FU) and its derivative, carmofur (HCFU), in cats was morphologically examined; both these drugs were orally administered once daily for a maximum of three months. The dosis of FU and HCFU was 2 mg/kg/day and 10 mg/kg/day, respectively. Both FU and HCFU induced two sorts of changes in the brain, i.e., vacuolation and softening-like change. The former was distributed in the white matter of the cerebrum and cerebellum and in areas of the gray matter such as the tectum and tegmentum of the brain stem, while the latter was distributed exclusively in the gray matter of the tectum and tegmentum of the brain stem. The tectum, especially the inferior colliculus, was most frequently affected by both types of change. Ultrastructurally, vacuolation was found to be due to lamellar splitting or separation between the axon and innermost myelin layer. These findings were compared with those in dogs and as the etiopathogenesis vacuolation due to direct toxic effect of FU or its metabolites to myelin and softening-like change due to local circulatory disturbance caused by vacuolation were proposed. ACTA PATHOL JPN 38: 1255-1266, 1988.     

卡莫氟与替加氟用于消化道肿瘤联合化疗的临床观察

目的：观察卡莫氟（HCFU）联合奥沙利铂（OXA）与替加氟＋亚叶酸钙（CF）联合奥沙利铂（OXA）治疗晚期消化道肿瘤的临床疗效与毒副作用。方法：52例晚期消化道肿瘤患者随机分为A、B两组,A组28例,采用卡莫氟＋奥沙利铂治疗,B组24例,采用替加氟＋亚叶酸钙＋奥沙利铂治疗。结果：A组的总有效率为68.00%,B组为39.13%,A组患者的总有效率明显高于B组（P〈0.05）;两组的中位疾病进展时间和中位生存期分别为17.8月、9.3月和19.6月、8.9月。主要不良反应为骨髓抑制、粘膜炎、恶心呕吐等,A组恶心呕吐的发生率明显低于B组（P〈0.05）。结论：卡莫氟联合奥沙利铂方案相比替加氟加亚叶酸钙联合奥沙利铂方案治疗晚期胃肠道肿瘤疗效更好,不良反应轻且安全,值得推广应用。     

Subacute leucoencephalopathy induced by carmofur,a 5-fluorouracil derivative

Summary Three cases of leucoencephalopathy induced by carmofur (1-hexylcarbamoyl-5-fluorouracil), an antineoplastic derivative of 5-fluorouracil are reported and the literature is reviewed. Initial symptoms were unsteady gait and dementia developing several weeks or months after carmofur had been started. Symptoms increased gradually even after stopping the drug. Severe encephalopathy with confusion, delirium or coma appeared frequently. Symptoms were usually reversible but death occasionally occurred. The EEG showed marked slowing. Computed tomography of the brains of severely intoxicated patients showed marked hypodensity of the entire cerebral white matter. Carmofur must be discontinued immediately if any psychomotor symptoms develop.Supported in part by grants-in-aid from the Ministry of Education, Science and Culture, and from the Ministry of Health and Welfare, Japan     

卡莫氟配合TACE治疗原发性肝癌的临床观察

目的探讨卡莫氟配合经肝动脉灌注化疗栓塞（TACE）治疗中晚期原发性肝癌的疗效。方法90例肝癌患者采用同期配对法分成两组,综合治疗组（试验组）45例,采用TACE＋卡莫氟,末次TACE术后2周口服卡莫氟,每次200 mg,每日3次,两周为1周期,间隔2周进行下一周期,共2-4周期;对照组45例,单纯采用TACE。TACE方案选择顺铂（DDP）60-100 mg、丝裂霉素（MMC）12-20 mg、5-Fu 1 000-1 500 mg,再将表柔比星（表阿霉素,EPI）50-70 mg与超液化碘油10-20 ml充分混合成乳剂缓缓注入,然后用1-2 mm的明胶海绵栓塞供血动脉,两组均行TACE2-3次。结果综合组（试验组）近期有效率91.1%,对照组60.0%,两组差异有非常显著性（χ2=11.79,P〈0.01）,综合组1,2,3,5年生存率分别为88.9%、55.6%、33.3%和20.0%,对照组分别为51.1%、37.8%、20.0%和0（χ2=6.65,P〈0.01）,中位生存期分别为27.3和16.7个月（χ2=4.75,P〈0.05）。肝功能A级和B级3年生存率分别为48.3%和6.3%（χ2=8.195,P〈0.01）;5年生存率分别为31．0％和0,χ2=4．42,P〈0．05）。结论 卡莫氟配合TACE为较好的治疗原发性肝癌的方法。     

顺铂并卡莫氟治疗晚期胃肠道恶性肿瘤的效果

目的 观察顺铂(DDP)并卡莫氟(HCFU)治疗晚期胃肠道恶性肿瘤的效果及毒性反应.方法 将120例晚期胃肠道恶性肿瘤病人随机分为2组,每组60例.治疗组病人应用DDP、HCFU化疗,对照组应用DDP、氟尿嘧啶(FU)、醛氢叶酸(CF)化疗,评价两组疗效和毒性反应.结果治疗组有效率为40.0%,对照组有效率为30.0%,两组比较差异有显著性(χ2=9.23,P<0.05).治疗组毒性反应较轻.结论 DDP并HCFU治疗晚期胃肠道恶性肿瘤疗效肯定,毒性反应轻,病人耐受性好.     

HPLC法测定卡莫氟片中氟尿嘧啶的含量

目的:采用高效液相色谱法测定卡莫氟片中氟尿嘧啶的含量。方法:以十八烷基硅烷键合硅胶为填充剂,以甲醇-0.25%醋酸溶液为流动相,检测波长为258 nm。结果:氟尿嘧啶在0.156 5～2.347 5μg.mL-1浓度范围内线性关系良好,氟尿嘧啶的检测限为0.16 ng。结论:该方法简便、快速、结果准确。     

放射合并口服卡莫氟治疗贲门癌 30例

[目的]探讨卡莫氟配合放射治疗贲门癌的增敏价值。[方法]对30例贲门癌患者采用常规放疗合并口服卡莫氟治疗。[结果]1、2、3年生存率分别为76.7%、46.7%及23.3%，治疗后血象无明显变化。腹泻、恶心呕吐不严重。[结论]口服卡莫氟对贲门癌放疗有增敏作用。可提高患者生存率和生活质量。     

Neuropathologic study on chronic neurotoxicity of 5-fluorouracil and its masked compounds in dogs

Summary 5-Fluorouracil (FU) and its masked compounds tegafur (FT) and carmofur (HCFU) were administered orally to Beagle dogs daily for 6 months, and their chronic neurotoxic effects were examined morphologically.In ten dogs that survived the 6-month treatment large vacuoles produced by splitting of the intraperiod line of myelin were observed in the fornix in the wall of the third ventricle. In severely affected dogs large vacuoles developed in the medial preoptic area, medial portion of the internal capsule, the area around the subthalamic nucleus and the mammillo-thalamic tract. Axons of myelinated fibers affected by vacuolation were generally well maintained, and destruction of myelin was not detected. Though proliferation of glia cells or abnormality of oligodendroglia was not detected, a lipid deposit covered by a single layer membrane was observed in the cell bodies and processes of astrocytes. No abnormality was detected by electron microscopy in the cerebrum, inferior colliculus, cerebellum, or pons. Of eight dogs that died during the treatment period, large vacuoles were observed in the fornix in the wall of the third ventricle of four dogs treated for more than 1 month, and large vacuoles were present in the inferior colliculus in two dogs of the FT group in the above four dogs. In the HCFU group, the interruption of treatment for 6months resulted in alleviation or disappearance of the vacuolar lesions. The above findings suggest that the neurotoxicity of FU and its masked compounds FT and HCFU in long-term treatment produces changes morphologically identical with one another in respect to the site of their manifestation and nature of lesion, that their common degraded product -fluoro--alanine (FBAL) plays a crucial role in their neurotoxic actions, and that vacuolar lesions, to which myelin was more vulnerable than neurons, can develop where the toxic substance readily deposits and accumulates.