The handling of anti-cancer drugs in elderly patients

The management of elderly patients with cancer is not established. The use of antineoplastic agents (particularly of chemotherapy) raises a lot of questions. Efficiency and toxicity. Data come from subgroups of clinical trials and from selected populations. Chronological age itself does not contra-indicate chemotherapy. Pharmacokinetics. Physiologic and functional changes occur with aging but there is great inter-patient variability. Oral chemotherapy. Oral treatments underline the problem of compliance. Under-treatment. Elderly patients are under-represented in clinical trials. Relevant issues have to be defined individually and cancer's real place in patient's general situation has to be specified. Geriatric assessment. This tool has proved its usefulness in many domains for global management of elderly patients. A multidisciplinary team is necessary, under geriatrician coordination. The aim is to elaborate an individualized medico-social intervention program. Geriatric assessment in oncology. Its interest for cancer patients is shown by emerging reports but its routine use by oncologists is impossible. Treatment strategies. They are not validated. Future: New clinical and pharmacokinetic studies are necessary in order to specify the place of the various tools and to enhance the handling of such molecules.     

The mutagenic activity of anti-cancer drugs and the urine of rats given these drugs

Summary Twenty-one anti-cancer drugs have been tested for their ability to cause mutations in Salmonella typhimurium test strains in the Salmonella/microsome mutagenicity test. Nine of the 21 anticancer drugs showed this ability: cyclophosphamide, nitromin, thio-tepa, busulfan, 6-mercaptopurine, neocarzinostatin, daunomycin, adriamycin and estramustine phosphate. Seven of these 9 mutagenic drugs were injected continuously into the jugular veins of rats. Urine was collected through a cystostomy tube and tested for mutagenicity. The urine from rats treated with 6 of these 7 drugs was mutagenic. These were cyclophosphamide, nitromin, thio-tepa, neocarzinostatin, adriamycin and daunomycin.     

Local anaesthetic drugs

Local anaesthetics (LA) are weak bases consisting of a lipophilic aromatic ring linked to a hydrophilic tertiary amine by either an ester or amide bond. It is this chemical link that enables classification of the LA. They exist in solution as an equilibrium of ionized and unionized forms. The unionized form is free to diffuse across the axonal membrane, but it is the ionized form which then binds and blocks the intracellular portion of the voltage gated sodium channel, preventing sodium influx and nerve transmission. Neuronal activity and nerve fibre diameter determine neuronal sensitivity; whereas pKa, lipid solubility, protein binding and inherent vasomotor activity affect the pharmacological properties of the LA. LAs can be administered by a variety of methods depending on clinical requirement including topical, local infiltration, intravenous and neuraxial and peripheral nerve blockade. While generally safe, the toxic effects of LAs can have wide-ranging effects including methaemoglobinaemia and systemic toxicity. The effects of ion trapping, stereoisomers, and additives have significant clinical consequences and require special consideration.     

Local anaesthetic drugs

Local anaesthetics (LA) are weak bases consisting of a lipophilic aromatic ring linked to a hydrophilic tertiary amine by either an ester or amide bond. It is this chemical link that enables classification of the LA. They exist in solution as an equilibrium of ionized and unionized forms. The unionized form is free to diffuse across the axonal membrane, but it is the ionized form which then binds and blocks the intracellular portion of the voltage gated sodium channel, preventing sodium influx and nerve transmission. Neuronal activity and nerve fibre diameter determine neuronal sensitivity; whereas pKa, lipid solubility, protein binding and inherent vasomotor activity affect the pharmacological properties of the LA. LAs can be administered by a variety of methods depending on clinical requirement including topical, local infiltration, intravenous and neuraxial and peripheral nerve blockade. While generally safe, the toxic effects of LAs can have wide-ranging effects including methaemoglobinaemia and systemic toxicity. The effects of ion trapping, stereoisomers, and additives have significant clinical consequences and require special consideration.     

Continuous intravenous administration of drugs

Continuous intravenous administration of drugs may be a problem in clinical practice; for several reasons patients do not always receive the dose of drug intended for them. Problems of parenteral fluid composition are related to the solvent, dilution and drug interactions. Physical factors influencing drug stability are light and adsorption onto perfusion sets. Examples are reported for each problem. A practical solution, based on personal experimentation, is proposed for diazepam and nitroglycerin administration.     

皮肤软组织扩张术中局部给药新途径的临床应用

为了皮肤扩张术顺利进行,缩短扩张时间、减少并发症,设计了同时放置埋入式药物注入器,以便随时在扩张过程中向局部注入强地松龙、普鲁卡因等药物的新方法,通过临床应用组与对照组比较,结果证明效果确切,方法简便实用,值得推广。     

皮肤软组织扩张术中局部给药新途径的临床应用

为了皮肤扩张术顺利进行，缩短扩张时间、减少并发症，设计了同时放置埋入式药物注入器，以便随时在扩张过程中向局部注入强地松龙、普鲁卡因等药物的新方法，通过临床应用组与对照组比较，结果证明效果确切，方法简便实用，值得推广。     

临床试验药品存放管理方法的改进

目的探讨改进临床试验药品存放管理方法的效果。方法将为期12个月的多中心药物临床试验的药品,前3个月按常规存放管理药品(对照组),后9个月采用改进方法存放管理药品(实验组),即为药物临床试验受试者划定出存放药品的药品库位并标上库位码,将试验药品对号摆放的同时做好取药引子。在应用过程中加强环节管理如加设有关累加统计表等。结果实验组取药时间显著短于对照组(P<0.01),回收药瓶和剩余药品盘点准确率高于对照组,且节省了盘点时间。结论改进临床试验药品存放管理方法,能提高取药时效,提高工作效率。     

皮肤软组织扩张术中局部给药新途径的临床应用

为了皮肤扩张术顺利进行，缩短扩张时间，减少并发症，设计了同时放置埋入了式药物注入器以便随时在扩张过程中向局部注入强地松龙，普鲁卡因等药物的新方法，通过临床应用组与对照组比较，结果证明效果确切，方法简便实用，值得推广。     

Effect of various anti-cancer drugs on human renal cell carcinoma serially transplanted into nude mice

Using two xenografts of human renal cell carcinomas serially transplanted in nude mice (AM-RC-1 and AM-RC-6), both of which maintained the basic histologic features of the original tumor and showed a constant growth rate, the effects of various anticancer agents against 2 target tumors were evaluated. MitomycinC (MMC), adriamycin (ADM), cisplatinum diaminodichloride (CDDP), 5-fluorouracil (5FU), 5-fluro-2'-deoxy-beta-uridine (FUDR) and human lymphoblastoid interferon (HLBI) against AM-RC-1, and MMC, ADM, CDDP, vinblastin (VBL) and etoposide (VP-16) against AM-RC-6. Drugs other than HLBI were administered 3 times in total every three to five days by intraperitoneal injection according to Battelle Columbus Laboratories Protocol and HLBI was injected daily for 10 days intraperitoneally. Anti-cancer effects were evaluated based on tumor growth curve and changes of histologic findings. In terms of tumor growth only MMC (in a dose of 3 mg/kg) revealed a statistically significant inhibitory effect against both AM-RC-1 and AM-RC-6 (respectively P less than 0.001 and P less than 0.05). Concerning AM-RC-1, a significant difference (P less than 0.01) was recognized in the ADM group (5 mg/kg) at the time of the second administration, but evaluation could not ultimately be done owing to appearance of acute toxity after the last dose. The most remarkable histologic changes by light microscopy were recognized in the MMC group (in a dose of 3 mg/kg) against AM-RC-1. They were degenerative findings such as intracellular and nuclear vacuolation, karyorrhexis, karyolysis, karyopyknosis and marginal hyperchromatosis, which corresponded to grade IIa of the classification of the National Cancer Center. The other drugs administered to AM-RC-1 exhibited only grade O to grade I changes. On the other hand, in AM-RC-6, histologic changes were mild (less than grade II) for all the drugs. Electron microscopic features were as follows. AM-RC-1: Marked increase of vacuole of organella was observed and lumens were filled with a large quantity of debris in MMC group (3 mg/kg). In the ADM group (5 mg/kg) there was debris in lumens, although almost no changes of organella were seen. CDDP groups (both 5.6 mg/kg and 2.8 mg/kg) showed autophagic vacuole in the cytoplasm and increased collagen fibers in the stroma but little changes of organella. AM-RC-6: Mild intracellular vacuolation was recognized in the MMC group (3 mg/kg). Watery degeneration and microfibrils were found in the cytoplasm in both ADM (5 mg/kg) and CDDP (5.6 mg/kg, 2.8 mg/kg) groups.     

Tetanic fade following administration of nondepolarizing neuromuscular blocking drugs

Fade in response to tetanic stimulation was studied following administration of atracurium 120 or 225 micrograms/kg, vecuronium 23 or 40 micrograms/kg, pancuronium 30 or 60 micrograms/kg, or d-tubocurarine 185 or 450 micrograms/kg. Ten patients received each dose and tetanic fade was measured at maximum block in the patients, who received the lower doses of the relaxants or at 10% recovery in those who received the higher doses. Fade during tetanic stimulation was generally similar in all the groups with the exception of the higher dose of pancuronium which showed a significantly greater fade in comparison with the higher doses of atracurium and d-tubocurarine. If fade in response to tetanic stimulation represents a prejunctional effect, the results from the present study suggest that neuromuscular blocking drugs cannot be differentiated with respect to their relative prejunctional effects by measurement of tetanic fade during established block after administration of clinically useful doses as used in the present study.