Advanced colorectal cancer in the elderly: results of consecutive trials with 5-fluorouracil-based chemotherapy

To evaluate toxicity and efficacy of chemotherapy in elderly patients (≥65 years of age) with advanced colorectal cancer, data from two consecutive trials conducted between 1984 and 1995 at the National Institute for Cancer Research were analysed comparing the results of treatment in those 65 years of age or older and in those younger than 65 years. Of 215 patients recruited, 82 elderly patients (median age 70 years, median performance status 1) received one of the following regimens based on 5-fluorouracil (5-FU): (1) weekly 5-FU 600 mg/m² i.v. bolus (30 patients); (2) weekly 5-FU 600 mg/m² bolus plus leucovorin (LV) 500 mg/m² 2-h i.v. infusion (28 patients); (3) Weekly 5-FU 2600 mg/m² 24-h continuous i.v. infusion plus LV 100 mg 4-h i.v. infusion and 50 mg orally every 4 h for five doses (24 patients). Overall, 1071 chemotherapy cycles were administered with a median number of 12 courses per patient. The main side effects were diarrhoea, observed in 38% of patients, stomatitis in 24% of patients and hand-foot syndrome in 13% of patients, and haematological toxicity affected only 15% of patients. No patient suffered grade IV toxicity. In three patients chemotherapy was discontinued because of toxicity (two patients suffered grade III diarrhoea, one patient grade III hand-foot syndrome). No significant difference in toxicity was evident between patients older than or younger than 65 years. Analysis of median dose intensity demonstrated no difference between the two groups. Overall objective response was observed in 18% (95% confidence limits 11–29) of elderly patients (15/82) in comparison with 23% (95% CL 17–32) of patients <65 years of age (31/133 pts). In conclusion, chemotherapy in elderly patients with advanced colorectal cancer is a safe and effective treatment with acceptable toxicity and comparable objective response rates. Received: 6 January 1998 / Accepted: 27 February 1998     

Superiority of hepatic arterial infusion in preventing catabolism of 5-FU compared with portal vein infusion revealed by an in vivo 19F NMR study

Purpose: The aim of this study was to identify the route of administration of 5-FU with the greatest pharmacological advantage in a rat model using noninvasive in vivo ¹⁹F nuclear magnetic resonance (NMR) spectroscopy. Methods: 5-FU (50 mg/kg) was administered to anesthetized Wistar rats cannulated into the hepatic artery, portal vein or tail vein and 11 NMR spectra were acquired from the liver region to 60.5 min every 5.5 min. Results: With systemic i.v. (tail vein) infusion, the ¹⁹F-NMR signal for 5-FU from the liver region peaked in the first spectrum (0–5.5 min), and then gradually decreased. The signal for the 5-FU catabolite α-fluoro-β-alanine (FBAL) gradually increased to the sixth spectrum (0–33.0 min) and then plateaued. Following portal vein infusion the intensity of the first 5-FU spectrum was twice as high as that following i.v. infusion, but the intensity decreased and the FBAL signal increased gradually in the sixth spectrum as systemic i.v. infusion. In contrast, the intensity of the 5-FU signal following hepatic artery infusion was the same as that following portal vein infusion in the first spectrum, and maintained a strong intensity to the final spectrum (60.5 min). The FBAL signal was detected from the second spectrum following hepatic artery infusion, but its intensity was significantly weaker than that following i.v. or portal vein infusion. Conclusions: Hepatic arterial infusion resulted in the active form of 5-FU being present for a longer time and its degradation in the liver being suppressed compared with the results following portal vein infusion. This catabolic advantage of hepatic areterial infusion could lead to a more potent anti-tumor activity against liver metastases, but could also lead to significant host toxicity including biliary toxicity. We recommend that the dose/schedule of 5-FU administered via the hepatic artery should be adjusted carefully. Received: 4 August 1997 / Accepted: 16 January 1998     

Supraventricular arrhythmia: A complication of 5-fluorouracil therapy

5-Fluorouracil is an S-phase-specific, synthetic pyrimidine antimetabolite, which is used as a cytostatic agent for a variety of malignant lesions, either singly or in multidrug regimens. Gastrointestinal toxicity and myelosuppression are the most common adverse reactions, but, of late, clinical cardiotoxicity has been reported in both prospective and retrospective studies. We present our experience of clinical cardiotoxicity in five patients.     

放疗联合化疗治疗复发直肠癌的临床研究

目的探讨放疗联合化疗治疗复发直肠癌的临床效果。方法对２９例根治术后复发的直肠癌进行了放射治疗，其中１６例同时给予大剂量醛氢叶酸（ＣＦ），氟脲嘧啶（５ＦＵ）的全身化疗（观察组），１３例为单纯放疗（对照组）。结果观察组中局部症状缓解率较对照组高，两组有效率分别为８１．２５％、４６．１６％，有显著性差异（Ｐ＜０．０５），完全缓解分别为１８．７５％、７．６９％。两组放疗引起的局部毒性反应相似。结论ＣＦ／５Ｆｕ配合放射治疗复发直肠癌可提高近期疗效，尤其对于伴远外转移患者为理想、安全的治疗手段。     

桂枝汤有效部位A对体温双向调节作用及其机理研究————对下丘脑NE、DA、5-HT含量的影响

在酵母诱导的发热大鼠中，桂枝汤有效部位Ａ（Ｆｒ．Ａ）能降低下丘脑５－ＨＴ、ＮＥ、ＤＡ含量；在安痛定诱导的低体温大鼠中，能升高５－ＨＴ含量。结果提示，Ｆｒ．Ａ为桂枝汤体温双向调节作用的一种物质基础，影响中枢神经递质５－ＨＴ的水平是其机理之一；其解热作用与影响中枢神经递质ＮＥ和ＤＡ的含量有关     

生脉散复方化学动态变化与药效关系的研究——生脉散复方化学的研究(Ⅰ)

为探讨生脉散全方独特疗效作用的物质基础，对其煎煮后的化学成分进行了研究。从生脉散合煎剂中分离得到一个复方产生的新成分，经ＵＶ，ＩＲ，ＭＳ及ＮＭＲ谱鉴定为５羟甲基２糠醛。研究表明，复方独特疗效有其独特的物质基础，与单味药及其简单加和在化学成分上有本质区别。从而阐明了中药配伍应用的合理性和科学性，并为制定复方制剂的质量检测提供了依据     

毛穗藜芦中茋类化合物的化学研究

目的：对毛穗藜芦根茎进行化学成分研究。方法：采用柱层析和薄层层析法进行分离，用ＵＶ，ＩＲ，ＭＳ，１ＨＮＭＲ等光谱技术鉴定化合物的结构。结果：得到２个类化合物，为白藜芦醇和２，３′，４，５′四羟基。结论：为首次从该植物中分离得到     

腺病毒介导的大肠杆菌CD自杀基因体内外对肿瘤杀伤作用的研究

编委会 Editorial Board名誉主编 Honorary Editor-in-chief吴孟超 Wu Meng chao(Second Military Medical University,Shanghai 200433学术顾问 Academic Advisers巴德年 Ba Denian(Chinese Academy of Medical Sciences,Beijing 100730)刘新垣 Liu Xinyuan(Shanghai Institute of Biochemistry,Chinese Academy of Sciences,Shanghai 200031)吴旻 WuMin(Cancer Institute,Chinese Academy of Medical Sciences,Beijing 100021)汤钊猷 Tang Zhaoyou(Shanghai Medical University,Shanghai 200032)主编 Editor-in-chief张友会 Zhang Youhui(Cancer Institute,Chinese Academy of Medical Sciences,Beijing,100021)副主编 Associate Editor-in-chief崔正言 Cul Zhenyan(Department of Immunology,Shandong Academy of Medical Sciences,Jinan 250001)钱振超 Qian Zhenchao(Department of Patho-physiology,Dalian Medical University,Dalian 116027)何球藻 He Qiuzao(Department of Immunology,Shanghai Medical University,Shanghai 200032)董志伟 Dong Zhiwei(Cancer Institute,Chinese Academy of Medical Sciences,Beijing 100021)常务副主编 Managing Editor-in-chief     

肺癌生存5年以上72例分析

[目的]探讨影响肺癌长期生存的因素。方法对1983年1月至1992年12月间收治的经病理证实的存活5年以上的72例肺癌患者进行分析。放疗采用60Co－r线或10MV－X线，大野前后对穿照射Dr40Gy/20次，共4周后缩野加量至总DT52G6y-76Gy（平均61．6Gy，非手术者）或50Gy－70Cy（平均56．1Gy，手术者）。手术均为肺叶（段）切除术。化疗主要方案为（CTX＋5－FU＋VCR、CTX＋ADM＋DDP、CTX＋5－FU＋CBP／E－ADM＋VP-16等。[结果]临床分期、病理类型和是否加用手术治疗对5年生存率的影响，分析显示有统计学差异。I、II、III、IV期5年生存率分别为42．9％、12．9％、5．8％及0；小细胞未分化癌与非小细胞癌的5年生存率分别为3．2％和96％；手术加放疗（加或不加化疗）与放疗（加或不加化疗）的5年生存率分别为对．5％和5．5％。而放疗剂量及是否加化疗对5年生存率的影响未显示有统计学差异。[结论]肺癌应进行早期诊断、早期治疗，尽量采取以手术为主的综合治疗，以提高远期生存率。     

羊红膻中新化合物──羊红膻醇的分离和鉴定

从陕西草药羊红膻Pimpinellathellungiana全草的正丁醇部分分得一个环乙烯类化合物（Ⅰ）和一个环乙醇类化合物（Ⅱ），经化学及光谱分析鉴定Ⅰ为3，4，5－trihydroxy－1－cyclohexene－1－carboxylicacid，即莽草酸（shikimicacid），Ⅱ为1－butyl－3，4，5－trihydroxy－cyclohexanol。Ⅰ为从该植物中首次得到，Ⅱ为一新化合物，定名为羊红膻醇（thellungianol）。