甲钴胺防治长春新碱神经毒性临床观察

目的：观察甲钴胺防治长春新碱神经毒性的近期疗效。方法：入选54例患者随机分为A、B两组,两组化疗方案均为含长春新碱1 mg/m2的化疗方案,21 d为1周期。A组（试验组）采用甲钴胺＋化疗,B组（对照组）单用化疗。A组在用长春新碱之前口服甲钴胺片0.5 mg/次,每日3次,第1~7 d,所有患者完成4周期化疗后评价疗效。结果：可评价病例54例,A组28例,发生神经毒性1级4例、2级2例、3级1例,总发生率25.0%。B组26例,发生神经毒性1级9例、2级4例、3级4例,总发生率65.4%。两组比较,差异有统计学意义（P〈0.05）。结论：甲钴胺能降低长春新碱神经毒性的发生率,值得临床推广应用。     

抗癌药1,2:5,6-二去水卫矛醇与长春新碱联合用药的实验研究

去水卫矛醇(DAG)与长春新碱(VCR)联合使用,对小鼠淋巴细胞白血病L₁₂₁₀有协同疗效,疗效强度决定于给药方案和剂量。先给DAG,24 h后给VCR,协同疗效最高。DAG剂量是影响疗效的主要因素,最佳剂量为3.0 mg/kg。琼脂扩散合试验亦证明二药有方案依赖性协同作用。二药合用对小鼠骨髓干细胞仅有微弱的协同杀灭作用。     

Severe vincristine toxicity in combination with itraconazole

We report two patients with acute lymphoblastic leukaemia (ALL) who were entered into the current MRC adult ALL trial (UKALL XII) in whom unusually severe vincristine induced neurotoxicity developed. This appeared to be the result of an interaction with itraconazole suspension.     

Cytotoxic Effects of Vitamin A in Combination with Vincristine, Daunorubicin and 6-Thioguanine upon Cells from Lymphoblastic Leukemic Patients

We studied whether isotretinoin potentiated the effects of vincristine (VCR), daunorubicin (DNR), and 6-thioguanine (6-TG) against cells obtained from 24 patients with acute lymphoblastic leukemia (ALL). Treatment with 5 μg /ml isotretinoin alone resulted in a leukemic cell survival of 82%± 28.1%. So isotretinoin is toxic to ALL cells. Dose-response curves were obtained for VCR, DNR and 6-TG in the presence and absence of isotretinoin Isotretinoin showed additive leukemic cell kills in combination with VCR and DNR, When corrected for cell kill by isotretinoin alone, it appeared that isotretinoin did not significantly enhance leukemic cell kills by VCR, DNR and 6-TG. No differences were found between samples from patients at initial diagnosis and at relapse with respect to cell kill by isotretinoin alone and with respect to a possible synergistic effect of isotretinoin and the cytostatic drugs. It is concluded that isotretinoin has additive antileukemic effects in combination with VCR or DNR. However, isotretinoin does not potentiate the antileukemic effects of VCR, DNR and 6-TG against leukemic cells obtained from patients with ALL.     

硫酸长春新碱在0.9%氯化钠注射液中的稳定性研究

本文用紫外分光光度法对硫酸长春新碱在０．９％氯化钠注射液中的稳定性，按经典恒温加速试验法进行了动力学实验研究，结果表明，硫酸长春新碱的降解为一级反应。２５℃，３２℃时硫酸长春新碱的有效期ｔ０．９分别为１２．５１ｈ，８．８６ｈ。为临床合理用药提供了确切的数据。     

Hyaluronidase as an antidote to extravasation ofVinca alkaloids: Clinical results

Skin necrosis is a recognized potential consequence of an inadvertent extravasation ofVinca alkaloids in the surrounding tissues during i.v. administration. Experimental studies suggest that hyaluronidase, an enzyme that degrades hyaluronic acid and improves the absorption of locally injected drugs, can reduce the risk of progressing to skin necrosis. On this basis, we used this enzyme as a local treatment after extravasations ofVinca alkaloids in seven patients. No patient suffered from subsequent skin necrosis. To the best of our knowledge, this is the first clinical report confirming the positive findings of experimental studies on the effectiveness of this antidote.     

Studies on the intracerebral injection of vincristine free and entrapped within liposomes in the rat

The cerebral tissue response and behaviour of rats injected with vincristine of increasing concentration, free and entrapped within liposomes was studied. In separate experiments, blood, urine and brain levels of vincristine were measured after intracerebral injection of free and liposome-entrapped vincristine. When entrapped within liposomes, vincristine clearance from the brain was significantly reduced and the amount of tissue damage was directly related to the amount of drug given, being slightly greater at the same dose when entrapped. These results indicate a potential application for drugs entrapped within liposomes acting as a depot preparation in the treatment of cerebral gliomas.     

Immunotherapy Maintenance in Acute Non-Lymphocytic Leukaemia

Abstract: Between January 1975 and December 1977, 264 adult patients with acute non-lymphocytic leukaemia entered the Australian National Leukaemia Trial. Of 251 evaluable patients, three induction regimens achieved similar complete response (CR) rates. CROP (cytosine arabinoside, daunorubicin, vincristine, prednisolone) produced CR in 41% of patients, 7 and 3 (cytosine arabinoside, daunorubicin) in 42% and 7 and 3 plus hydroxyurea in 52%. Remission duration and survival were similar when induction regimens were compared. Fortyfive patients reaching maintenance therapy were randomised to either chemo-immunotherapy (BCG plus intradermal leukaemic blast cells) or chemotherapy alone. The duration of CR in these two groups was almost identical, though patients receiving chemotherapy alone had prolonged survival (median 161 weeks) when compared to the chemo-immunotherapy group (84 weeks, p = 0.07). Institutions with less developed supportive facilities reported lower CR rates (p =0.04). Leucocytosis, (> 100 × 10⁹/I) and older age (> 50 years) were associated with shortened survival. The Trial has failed to show any advantage for this form of immunotherapy.     

Platelet size distribution in mice following immunothrombopenia and vincristine administration

Summary In the present study platelet size distribution was investigated after induction of immunothrombocytopenia by rabbit-anti-mouse-platelet-serum (RAMPS) and after vincristine-induced thrombocytopenia.The platelet size distribution after a single dose of RAMPS showed a shift to larger volumes at day 1 and 2, and a decrease to slightly smaller volumes than normal at day 8. These differences, however, were not statistically significant.After vincristine administration, a dose-dependent increase of the platelet size distribution was demonstrated, which lasted from day 1–7.It is suggested that in immune-induced thrombocytopenia the young platelets released from bone marrow megakaryocytes are not exclusively large platelets. On the other hand the early appearance of large platelets after vincristine administration points to a toxic or segregating effect of vincristine on circulating platelets. Therefore, in our experiments, the platelet size is not suitable for the differentiation of young and old platelets.This study was supported by the Deutsche Forschungsgemeinschaft. Qu 33/1