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1.
Vincristine has been in clinical use for over 40 years with initial publication of the results from successful trials in 1962. Catastrophic neurotoxicity has been associated with the administration of vincristine directly into the cerebrospinal fluid (CSF). Since the first case in 1968 there have been numerous other instances, of which 23 have been reported in the literature. Of these cases 18 resulted in death. The most prominent damage on autopsy was generally in the spinal cord, brain stem and cerebellum, with severity tending to be greater in the neurons adjacent to the CSF. Fatalities appeared due to a progressive ascending myeloencephalopathy. Early recognition and immediate treatment with CSF drainage and intrathecal exchange appears to be the only intervention that has improved patient survival. The volume of injection, dose and time from the incident until the ventriculo‐lumbar washout appear critical, as these factors might contribute to the extent of drug distribution in the CNS. Although several antidotes for vincristine have been suggested, including folinic acid and glutamic acid, supportive evidence for their effectiveness is scant. Several recommendations regarding prevention of this catastrophic event have been proposed. 相似文献
2.
Summary The devastating neuropathological changes wrought by the intrathecal administration of vincristine are reported, with a detailed account of the widespread lesions in the brain and spinal cord, found in post-mortem light- and electron-microscope studies. 相似文献
3.
R. Metz M. Delgado R. Keiling P. Cappelaere J. P. Armand G. Prevot J. L. Misset J. Grimbert G. Mathe 《Investigational new drugs》1985,3(2):163-166
Summary In our wide experience of treating advanced breast carcinoma with chemotherapy, the combination of doxorubicin (DOX), vincristine (VCR), cyclophosphamide (CPM) and fluorouracil (FU) gave a complete plus partial response rate of over 60%, with 100% alopecia and frequent cardiac toxicity depending on total dose.After the EORTC Clinical Screening Group phase II trial we have conducted an expected difference method comparative phase II trial using the combination DOX, VCR, CPM, FU and the combination of MTX (10mg/m2), VCR, CPM and FU on a population of 50 breast carcinoma patients similar to those taking part in the first study.The reasons for similarity of action will be presented and discussed. 相似文献
4.
K562及K562/VCR对长春新碱诱导凋亡的敏感性 总被引:1,自引:0,他引:1
研究人类白血病细胞株K562及耐长春新碱的K562变异株K562/VCR对长春新碱诱导凋亡的敏感性的差异,以探讨抗凋亡在白血病多药耐药性(MDR)中的作用。方法将K562及K562/VCR分别用浓度为0、0.001、0.010μg/ml的长春新碱诱导24h,用流式细胞仪PI染色法、TUNEL法及ELISA法分别进行细胞凋亡检测。结果经浓度为0、0.001μg/ml长春新碱诱导后,K562细胞凋亡率分别为(4.10±0.17)%、(13.30±3.74)%,而K562/VCR细胞凋亡率分别为(3.61±0.69)%、(9.06±4.24)%,统计学显示两者差异无显著性(n=3,P>0.05)。而长春新碱浓度达0.010μg/ml时,K562及K562/VCR细胞凋亡率分别为(36.48±6.70)%、(10.45±3.71)%,两者差异有极显著意义(n=3,P<0.01)。TUNEL及ELISA检测结果与此类似。结论K562及K562/VCR对长春新碱诱导细胞凋亡的敏感性不同,耐药细胞对药物诱导细胞凋亡的抵抗性增强可能在白血病MDR发生中有重要作用。 相似文献
5.
Barbara Kiburg Carry M. Moorer-van Delft Jan J. Heimans Peter C. Huijgens Harry H. Boer 《Journal of neuro-oncology》1996,30(3):173-180
Summary The use of the cytostatic agent vincristine (VCR) is limited by the occurrence of peripheral neuropathy. This side-effect is probably caused by interference with axonal microtubules. VCR depolymerizes microtubules and reacts with tubulin to form paracrystals. The potential of a neurotrophic ACTH(4–9) analogue, Org 2766, to counteract peripheral neuropathy caused by cytostatic agents is being investigated. In the present ultrastructural study, modulatory effects of Org 2766 on VCR-induced neurotoxicity were studied in vivo in neurons of the pond snail Lymnaea stagnalis, which has been shown previously to be a suitable test system to investigate neurotoxic side-effects of cytostatic agents. 24 h after treatment with VCR (25 M), 68.4 ± 34.7 paracrystals were counted per cross-section of the cerebral commissure and the number of microtubules in the axons had been lowered to 46% of the control level. After a survival period of two weeks all paracrystals had disappeared. By that time, no recovery of the axonal microtubular system could be observed. However, post-treatment with Org 2766 (10–6 M) on day 6 after VCR treatment had induced a significant increase in the number of microtubules (+ 55%) on day 7. This beneficial effect lasted for the rest of the experimental period (14 days). These results suggest that post-treatment with Org 2766, i.e. after VCR clearance, can induce long-lasting beneficial effects on VCR-induced neurotoxicity in vivo. 相似文献
6.
Michele Baccarani Giovanna Corbelli Sante Tura S. Tura G. Corbelli M. Fiacchini M. Gobbi L. Gugliotta F. Lauria P. Ricci A. Zaccaria M. Baccarani F. Mandelli G. Alimena G. Papa L. Annino G. Guglielmi A. Allegra 《Leukemia research》1981,5(2):149-157
The effect of early splenectomy and of polychemotherapy with hydroxyurea, busulfan, and alternate bimonthly courses of arabinosyl cytosine and vincristine plus prednisone, was evaluated in 139 previously untreated patients with chronic myeloid leukemia (CML), consecutively admitted to 18 hospitals from March 1973 to October 1974. Fifty-six patients were splenectomized and 83 patients were not splenectomized. Splenectomy did not influence the duration of chronic and blastic phase, and did not prolong survival. The prognosis of high risk patients was not improved. During the chronic phase, high platelet counts were more frequent in splenectomy group, and five patients developed thrombotic or thromboembolic complications, 5 to 19 months after the operation. The median survival of the whole group was 50 months, with 32 of 139 patients (actuarial proportion 30%) remaining alive 72 months after diagnosis, but the slope of the survival curve was similar to that of historical controls. The results of this trial suggests that new strategies should be developed for the therapy of CML. 相似文献
7.
8.
Hellman Richard Neuberg Donna S. Wagner Henry Grunnet Margaret Robins H. Ian Karp Daniel Flynn Patrick Adams George 《Journal of neuro-oncology》1998,37(1):55-62
This study is a combined modality Phase II therapeutic trial to determine the efficacy of the novel combination of VP-16, Vincristine and Procarbazine in addition to postoperative radiation therapy in patients with high grade intracranial gliomas. Thirty three patients (median age 51 years) were entered (27 with glioblastoma multiforme, 6 with anaplastic astrocytoma). Toxicity was manageable with no lethal toxicities. Five of seven life threatening toxicities were hematologic. Median overall survival was 14.2 months. These data suggest this regimen is effective treatment for patients with high grade gliomas. 相似文献
9.
硫酸长春新碱传递体的制备及其离体透皮研究 总被引:7,自引:0,他引:7
目的:筛选制备硫酸长春新碱传递体(VCR-T)的最佳工艺,预测其作为VCR新制剂的可行性。方法:采用干膜超声法通过正交试验优化制备工艺;激光散射粒径分析仪测量粒径及其分布,透射电镜观察形态,HPLC测定包封率;改良的Franz扩散池进行体外透皮试验。结果:最优处方及工艺:卵磷脂:去氧胆酸钠为70:20,载体:VCR为45:10;pH7.3,水合30min;制备的硫酸长春新碱传递体为淡黄色透明胶体溶液,平均粒径94nm,外形圆整光滑,分布均匀,包封率为90%;以零级速率透过皮肤,24h累积透皮吸收率为63.8%。结论:VCR-T有望成为VCR临床给药的一种新给药系统。 相似文献
10.
氨磷汀对化疗药物抗卵巢癌细胞的影响 总被引:1,自引:0,他引:1
目的评价细胞保护剂氨磷汀(amifostine)对不同化疗药物抗卵巢癌细胞的影响。方法用MTT法分别测定顺铂、长春新碱、依托泊甙和丝裂霉素对体外培养的Ho-8910肿瘤细胞系的抑制作用,实验组加化疗药前30 min经600mg.L-1氨磷汀处理,对照组不用氨磷汀处理,余同实验组,培养后比较两组细胞增殖的抑瘤率。结果实验组与对照组比较,两组肿瘤细胞抑制率无显著性差异(P>0.05)。结论氨磷汀不影响顺铂、依托泊甙、丝裂霉素和长春新碱对Ho-8910肿瘤细胞的抑制作用。 相似文献