Abstract
The mechanisms of action underlying the neurotoxicity caused by chemotherapeutic drugs can be related to the mechanism by which the drug exerts its anticancer activity, but may also be totally different. In order to be able to study these mechanisms, the development and use of in-vitro and in-vivo test models are indispensable. In addition, the models may provide a preclinical tool to test possible methods for prevention and treatment of drug-related neurotoxicity. In the first place, it can be stated that the number of available models is small, whereas most of the existing models can be strictly applied only to a specific class of anticancer drugs. Another aspect, of equal importance, is the often underestimated influence of pharmacological parameters, such as the route of administration, the kinetics of the drug and drug interactions.
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References
Rosenberg B: Fundamental studies with cisplatinum. Cancer 1985 (55):2303–2316
Filipski J, Kohn KW, Bonner WM: The nature of inactivating lesions produced by platinum (II) complexes in phase lambda DNA. Chem Biol Interactions 1980 (32):321–330
Srivastava RC, Froehlich J, Eichhorn GL: The effect of platinum binding on the structure of DNS and its function in RNA synthesis. Biochimie 1978 (60):879–891
Stone PS, Kelman AD, Sinex FM: Specific binding of antitumour durg cis-Pt (NH3) 2C12 to DNA rich in guanine and cytosine. Nature 1974 (251):736–737
Roberts JJ, Fravel HNA: The interaction of antitumour platinum compounds with cellular DNA in cultured cells and animal tissues: relationship to DNA cellular repair processes. Biochimie 1978 (60):869–877
Roelofs Rl, Hrushesky W, Rogin J, Rosenberg L: Peripheral sensory neuropathy and cisplatin chemotherapy. Neurology 1984 (34):934–938
Thompson SW, Davis LE, Kornfeld M, Hilgers RD, Standefer KJC: Cisplatin neuropathy: clinical, electrophysiological, morphologic and toxicologic studies. Cancer 1984 (54):1269–1275
Thomas PK, Olsson Y: Connective tissue components of peripheral nerve. In: Dyck et al (eds) Peripheral Neuropathy. Saunders, Philadelphia 1984 pp 111–120
Terheggen PMAB, Gerritsen van der Hoop R, Floot BGJ, Gispen WH: Cellular distribution of cisdiamminedichloroplatinum (II)-DNA binding in rat dorsal root spinal ganglia: effect of the neuroprotecting peptide Org 2766. Toxicol Appl Pharmacol 1989 (99):334–343
Muller LJ, Gerritsen van der Hoop R, Moorer-van Delft CM, Gispen WH, Roubos EW: Morphological and electrophysiological study of the effects of cisplatin in Org 2766 on rat spinal ganglion neurons. Cancer Res (in press)
Tomiwa K, Nolan C, Cavanagh JB: The effects of cisplatin on rat spinal ganglia: a study by light and electron microscopy and by morphometry. Acta Neuropathol 1986 (69):295–308
Stewart D, Montpetit V, Mikhael N et al: Cisplatin neuropathy. Proc AACR 1989 (30):246
Stewart DJ, Wallace S, Feun L et al: A phase I study of intracarotid artery infusion of cisdiammindichloroplatinum (II) in patients with recurrent malignant intracerebral tumors. Cancer Res 1982 (42):2059–2062
Neuwelt EA, Barnett PA, Glassberg M, Frenkel EP: Pharmacology and neurotoxicity of cisdiamminedichloroplatinum, bleomycin, 5-fluorouracil and cyclophosphamide administration following osmotic blood-brain barrier modification. Cancer Res 1983 (43):5278–5285
Gormley PE, Gangji D, Wood JH, Poplack DG: Pharmacokinetic study of CNS penetration of cisdiaminedichloro platinum. Cancer Chemother Pharmacol 1981 (5):257–260
De Koning P, Neijt JP, Jennekens FGI, Gispen WH: Evaluation of Cis-Diamminedichloroplatinum (II) (cisplatin) neurotoxicity in rats. Toxicol Appl Pharmacol 1987 (89):81–87
Gastaut JL, Pellisier JF: Neuropathie au cisplatine: etude clinique, électrophysiologique et morphologique. Rev Neurol 1985 (141):614–626
Rebert CS, Pryor GT, Frick MS: Effects of vincristine, maytansine, and cis-platinum on behavioral and electrophysiological indices of neurotoxicity in the rat. J Appl Toxicol 1984 (4):330–338
Gerritsen van der Hoop R, Neijt JP, Kennekens FGI, Gispen WH: Protection from cisplating induced neuropathy in rats by the ACTH (4-9) analog Org 2766. In: Pleasure D, Fiori M, Scarlato G, Scarpini E (eds) Proc. Peripheral Nerve Development and Regeneration. Livinia, Springer Verlag 1989 (19) pp 145–148
Gerritsen van der Hoop R: Prevention and treatment of cisplatin-induced neurotoxicity by Org 2766, and ACTH (4-9) analog. Thesis, Utrecht, 1989 pp 82–92
Elderson A, Gerritsen van der Hoop R, Haanstra W, Neijt JP, Gispen WH, Jennekens FGI: Vibration perception and thermoperception as quantitative measurements in the monitoring of cisplatin induced neuropathy. J Neurol Sci 1989 (93):167–174
De Koning P, Neijt JP, Jennekens FGI, Gispen WH: Org 2766 protects from cisplatin induced neurotoxicity in rats. Exp Neurol 1988 (97):746–750
Gerritsen van der Hoop R, De Koning P, Boven E, Neijt JP, Jennekens FGI, Gispen WH: Efficacy of the neuropeptide Org 2766 in the prevention and treatment of cisplatin-induced neurotoxicity in rats. Eur J Cancer Clin Oncol 1988 (24):637–642
Gerritsen van der Hoop R, Vecht ChJ, Van der Burg MEL, Elderson A, Boogerd N, Hermans JJ, Vries JC, van Houwellin G, Jennekens FGI, Gispen WH, Neijt JP: Org 2766, an ACTH (4-9) analog, prevents cisplatin induced neuropathy in ovarian cancer patients. N Engl J Med 1990 (322):89–94
Mollman, Glover J, Hogan M, Furman RE: Cis Platin Neuropathy. Risk factors, prognosis and protection by WR-2721. Cancer 1988 (61 ):2192–2195
Hoeve LJ, Mertens zur Borg IRAM, Rodenburg M, Brocaar MP, Groen BGS: Correlation between cisplatinum dosage and toxicity in a guinea pig model. Arch Otorhinolaryngol 1988 (245):98–102
Baranak CC, Wetmore RF, Packer RJ: Cis-platinum ototoxicity after radiation treatment: an animal model. J Neurooncol 1988 (6):261–267
Granowetter L, Rosenstock JG, Packer RJ: Enhanced cis-platinum neurotoxicity in pediatric patients with brain tumors. J Neurooncol 1983 (1):293–297
Wagstaff AJ, Ward A, Benfield P, Heel RC: Carboplatin: a preliminary review of its pharmacodynamics and pharmacokinetic properties and therapeutic efficacy in the treatment of cancer. Drugs 1989 (37):162–190
Boven E, Van Der Vijgh WSF, Nauta MM, Schluper HMM, Pinedo HM: Comparative activity and distribution studies of five platinum analogues in nude mice bearing human ovarian carcinoma xenografts. Cancer Res 1985 (45):86–90
Bhattacharyya B, Wolff J: Membrane-bound tubulin in brain and thyroid tissue. J Biol Chem 1975 (250):7639–7646
Hemminski K: Effects of colchicine and cytochalasin B on labelling and enzyme activities of brain plasma membranes. Int J Neurosci 1973 (6):159–163
Hindelang-Gertner C, Stoeckel ME, Porte A, Stertinsky F: Colchicine effects on neurosecretory neurons and other hypothalamic and hypophysial cell, with special reference to changes in the cytoplasmic membranes. Cell Tiss Res 1976 (170):17–41
Geraerts WPM, Ter Maat A, Vreughdehil E: The peptidergic neuroendocrine control of egg-laying behavior in Aphysia and Lymnea. In: Laufer H, Downer R (eds) Inter Vertebrate Endrocrinology. AR Liss Inc.,New York 1988 (Vol. 2) pp 141–231
Green LS, Donoso JA, Heller-Bettinger IE, Samson FE: Axonal transport disturbances in vincristineinduced peripheral neuropathy. Ann Neurol 1977 (1):255–262
Goldschmidt RB, Steward O: Comparison of the neurotoxic effects of colchicine, the vinca alkaloids and other microtubule poisons. Brain Res 1989 (486):133–140
Dustin P: Microtubules. Springer-Verlag London, Heidelberg 1978
Schlaepfer WW: Vincristine-induced axonal alterations in rat peripheral nerve. J Neuropathol Experim Neurol 1971 (30):488–505
Donoso JA, Green LS, Heller-Bettinger IE, Samson FE: Action of the vinca alkaloids vincristine, vinblastine, and desacetyl vinblastine amide on axonal fibrillar organelles in vitro. Cancer Res 1977 (37):1401–1407
Muller LJ, Moorer van Delft CM, Roubos EW: Snail neurons as a possible model for testing neurotoxic side effects of antitumour agents: Paracrital formation by vinca alkaloids. Cancer Res 1988 (48):7184–7188
Menesini Chen MG, Chen JS, Calissano P, Levi Montalcini R: Nerve growth factor prevents vinblastine destructive effects on sympathetic ganglia in newborn mice. Proc Natl Acad Sci 1977 (74):5559–5563
Owellen RJ, Owens AH, Donigan DW: The binding of vincristine, vinblastine and colchicine to tubulin. Biochem Biophys Res Commun 1972 (47):685–691
Takasugi BJ, Jones SE, Robertone AB: Phase II trial of vinzolidine, an oral vinca alkaloid, in Hodgkin‘s disease and non-Hodgkin’s lymphoma. Cancer Treat Rep 1984 (68):1399–1401
Binet S, Fellows A, Lataste H, Krikorian A, Couzimier JP, Meininger V: In situ analysis of the action of navelbine on various types of microtubules using immunofluorescence. Semin Oncol 1989 (16):5–8
Gerzun K, Ochs S, Todd GG: Polarity of vincristine, vindasine and vinblastine in relation to neurological effects. Proc Am Assoc Cancer Res 1979 (20):46
Nelson RL, Dyke RW, Root MA: Comparative pharmacokinetics of vindesine, vincristine and vinblastine in patients with cancer. Cancer Treat Rev 1980 (7):17–24
Noble RL, Gout PW, Wijcik LL, Hebden HF, Beer CT: The distribution of 3Hvinblastine in tumor and host tissues of Nb rats bearing a transplantable lymphoma which is highly sensitive to the alkaloid. Cancer Res 1977 (37):1455–1460
Jackson DV, Sethi VS, Spurr CL, McWorther JM: Pharmacokinetics of vincristine in the cerebrospinal fluid of humans. Cancer Res 1981 (41):1466–1468
Jackson DV, Castle MC, Poplack DG: Pharmacokinetics of vincristine in the cerebrospinal fluid of sub-human primates. Cancer Res 1980 (40):722–724
Gaidys WG, Dickerman JD, Walters CL, Young PC: Intrathecal vincristine: Report of a fatal case despite CNS washout. Cancer 1983 (52):799–801
Letourneau PC, Ressler AH: Inhibition of neurite initiation and growth by taxol. J Cell Biol 1984 (98):1355–1362
Masurovsky EB, Peterson ER, Crain SM, Horfowitz SB: Microtubule arrays in taxol treated mouse dorsal root ganglia-spinal cord cultures. Brain Res 1981 (217):392–398
Parnass J, Horowitz SB: Taxol binds to polymerized in vitro. J Cell Biol 1981 (91):479–487
Slotwiner P, Song SK, Anderson PJ: Spheromembrenous degeneration of muscle induced by vincristine. Arch Neurol 1966 (15):172–176
Graff GLA, Geuning C, Hildebrand J: Action de sulfate de vincristine sur le gastrocnemien du rat II. Effects indépendants de Palcaloide et de la dénervation motrice sur le métabolisme des phosphates inorganismes, organiques acidosoluble et des phosphalipides. Cr Soc Biol 1966 (162):588–593
Gottschalk PG, Dyck PJ, Kiely JM: Vinca alkaloid neuropathy: nerve biopsy studies in rats and in men. Neurology 1968 (18):875–882
Norido F, Finesso C, Fiorito P, Marino P et al: General toxicity and peripheral nerve alterations induced by chronic vincristine treatment in rabbit. Toxicology Appl Pharmacol 1988 (93):433–441
Muller U, Moorer-Van Delft CM, Roubos EW: Snail neuron as a possible model for listing neurotoxic side effects of antitumor agents. Paracristal formation by vinca alkaloids. Cancer Res 1988 (48):7184–7188
Favaro G, Di Gregorio F, Panazzo C, Fiori MG: Ganglioside treatment of vincristine-induced neuropathy. An electrophysiologic study. Toxicology 1988 (49):325–329
Hellmann K, Hutchinson GE, Henry K: Reduction of vincristine toxicity by cronasial. Cancer Chemother Pharmacol 1987 (20):21–25
Jackson DV Jr, Rosenbaum DL, Carlisle LH, Long TR, Wells HG, Spurr CL: Glutamic acid modifications of vincristine toxicity. Cancer Biochem Biophys 1984 (7):245–252
Jackson DV, Wells HB, Atkins JN, Zekan PJ, White DR, Richards F, Gruz JM, Muss HM: Amelioration of vincristine neurotoxicity by glutamic acid. Am J Med 1988 (84):1016–1022
Jolivet J, Cowan KH, Curt GA, Clendenin NJ, Chabner BA: The pharmacology and clinical use of methotrexate. N Engl J Med 1983 (3):1094–1104
Chabner BA, Allegra CJ, Curt GA, Clendeninn NJ, Baram J, Koizumi S, Drake JC, Jolivet J: Polyglutamation of methotrexate. J Clin Invest 1985 (76):907–912
Pinedo HM, Chabner BA: Role of drug concentration, duration of exposure and endogenous metabolites in determining methotrexate cytotoxicity. Cancer Treat Rep 1977 (61):709–715
Gangji D, Ducore J, Poplack D, Kohn K, Glaubiger D: Concentration and time dependance of methotrexate cytotoxicity in mouse L1210 leukemia cells and human Burkitt’s lymphoma cells. Clin Res 1980 (28):525
Goldie JH, Price LA, Harrap KR: Methotrexate toxicity: correlation with duration of administration, plasma level doses and excretion pattern. Eur J Cancer 1972 (8):409–414
Ackland SD, Schilsky RL: High-dose methotrexate: a critical reappraisal. J Clin Oncol 1987 (5):2017–2031
Bleyer WA: Neurological sequelae of methotrexate and ionising. A new classification. Cancer Treat Rep 1981 (65):89–98
Price RA, Jamieson PA: The central nervous system in childhood leukemia. II subacute leukoencephalopathy. Cancer 1975 (35):306–318
Rubinstein LJ, Herman MM, Long TF, Wilbur JR: Disseminated necrotizing leukoencephalopathy: a complication of treated central nervous system leukemia and lymphoma. Cancer 1975 (35):291–305
Gangji D, Reaman GH, Cohen SR, Bleyer WA, Poplack DG: Leukoencephalopathy and elevated levels of myelin basic protein in the cerebrospinal fluid of patients with acute lymphoblastic leukemia. N Engl J Med 1980 (303): 19–21
Price RA: Therapy related central nervous system diseases in children with acute lymphocytic leukemia. In: Mastrangelo R, Poplack DG, Riccardi R (eds) Central Nervous system Leukemia Prevention and Treatment. Martinus Nijhof, Boston 1983 pp 71–83
Allen JC, Rosen G, Metha BM: Leucoencephalopathy following high-dose IV methotrexate with leucovorin rescue. Cancer Treat Rep 1980 (64):1261 -1273
Neijstrom E, Gabriel DA: High-dose methotrexateinduced neurotoxicity associated with elevation of CSF myelin basic protein. J Clin Oncol 1985 (3):593–594
Yap H, Blumenshein GR, Yap BS: High-dose methotrexate for advanced breast cancer. Cancer Treat Rep 1979 (63):757–761
Wernick R, Smith: Central nervous system toxicity associated with weekly low-dose methotrexate treatment. Arthritis Rheum 1989 (32):770–775
Geieser CF, Bishop Y, Jaffe N, Furman L, Traggis D, Frei E: Adverse effects of intrathecal methotrexate in children with acute leukemia in remission. Blood 1975 (45):189–195
Nathan PW, Sears TA: Action of methylhydroxybenzoate on nervous conduction. Nature 1961 (192):668–669
Hahn AF, Feasby TE, Gilbert JJ: Paraparesis following intrathecal chemotherapy. Neurology 1983 (33):1032–1038
Dutera MJ, Bleyer WA, Pomeroy TC, Leventhal C, Leventhal BG: Irradiation, methotrexate toxicity and the treatment of meningeal leukemia. Lancet 1971 (1):703–772
Bleyer WA, Drake JC, Chabner BA: Neurotoxicity and elevated cerebrospinal fluid methotrexate concentration in meningeal leukemia. N Engl J Med 1973 (289):770–773
Bleyer WA, Poplack DG, Simon RM: Concentration x time methotrexate via a subcutaneous reservoir: a less toxic regimen for intraventricular chemotherapy of central nervous system neoplasms. Blood 1978 (51):835–842
Bleyer WA, Savitch JL, Holcenberg JS: An improved regimen for intrathecal chemotherapy. Clin Pharmacol Exp Ther 1976 (19):103–104
Dufner PK, Cohen ME, Brecher ML, Berer D, Parthasarathy KL, Bakshi S, Ettinger LF, Freeman A: CT abnormalities and altered methotrexate clearances in children with CNS leukemia. Neurology 1984 (34):229–233
Morse M, Savitch J, Balis F, Miser J, Feusner J, Reaman G, Poplack DG, Bleyer AW: Altered central nervous system pharmacology of methotrexate in childhood leukemia: Another sign of meningeal relapse. J Clin Oncol 1985 (3):19–24
Grossman SA, Chen DCP, Thompson G: Cerebrospinal fluid abnormalities in patients with the neoplastic meningitis. An evaluation using “indium-DTPA ventriculography”. Am J Med 1982 (73):641–647
Lampkin BC, Higgins GR, Hammond D: Absence of neurotoxicity following massive intrathecal administration of methotrexate. Cancer 1967 (20):1780–1781
Bates SE, Raphaelson Ml, Price RA, McKeever P, Cohen S, Poplack DG: Ascending myelopathy after chemotherapy for central nervous system acute lymphoblastic leukemia: Correlation with cerebrospinal fluid myelin basic protein. Med Ped Oncol 1985 (13):4–8
Ochs JJ, Berger P, Brecher ML, Sinks LF, Kinkel W, Freeman Al: Computed tomography brain scans in children with acute lymphocytic leukemia receiving methotrexate alone as central nervous system prophylaxis. Cancer 1980 (45):2274–22
Shapiro WR, Chernik NL, Posner JB: Necrotizing encephalopathy following intraventricular instillation of methotrexate. Arch Neurol 1973 (28):96–102
Yanovski JA, Packer RJ, Levine JD, Davidson TL, Micalizzi M, D’Angio G: An animal model to detect the neuropsychological toxicity of anticancer agents. Med Ped Oncol 1989 (17):216–221
Griffin TW, Rasey JS, Bleyer WA: The effect of photon irradiation on blood-brain permeability to methotrexate in mice. Cancer 1977 (40):1109–1113
Kamen BA, Moulder JE, Kun LE, Ring LE, Adams SM, Fish BL, Holcenberg JS: Effects of single dose and fractionated cranial irradiation on rat brain accumulation of methotrexate. Cancer Res 1984 (44):5092–5094
Veninga TS, Dankert J, Ebels EJ, Fidler VJ: Early transient accumulation of methotrexate in the cerebrospinal fluid. Act Radiol Oncol 1984 (23):69–73
Taylor EM, Geyer JR, Milstein JM, Shaw CM, Gerac JP, Wotton P, Hubbard BA, Bleyer AW: Rodent model of chemoradiotherapy-induced white matter necrosis. NCI Monograph 1988 (6):59–64
van der Kogel AJ, Sissingh HA: Effects of intrathecal methotrexate and cytosine arabinoside on the radiation tolerance of the rat spinal cord. Radiother and Oncol 1985 (4):239–254
Suzuki K, Takemura T, Okeda R, Hatakeyama S: Vascular changes of methotrexate-related disseminated necrotizing leukoencephalopathy. Acta Neuropathol 1984 (65):145–149
Lampert PW, Tom Ml, Rider WD: Disseminated demyelination of the brain following Co 60 (gamma) radiation. Arch Pathol 1959 (68):322–330
Gilbert MR, Harding BL, Grossman SA: Methotrexate neurotoxicity: in vitro studies using cerebellar explants from rats. Cancer Res 1989 (49):2502–2505
Grossman SA, Reinhard CS: The intracerebral penetration of intraventricularly administered chemotherapeutic agents: a quantitative autoradiographic study. Proc Amer Assoc Cancer Res 1985 (26):923
Burch PA, Grossman SA, Reinhard CS: Spinal cord penetration of intrathecally administered cytarabine and methotrexate a quantitative audiographic study. J Natl Cancer Inst 1988 (80):1211–1216
Royds JA, Lilleyman JS, Timperley WR, Taylor CB: Cerebrospinal fluid enolase isoenzymes and neurotoxicity in early treatment of lymphoblastic leukemia. Archives of Dis Child 1984 (59):266–269
Abelson HT: Methotrexate and central nervous system toxicity. Cancer Treat Rep 1978 (62):1999–2001
Winick NJ, Kamen BA, Balis FM, Holcenberg J, Lester CM, Poplack DG: Folate and methotrexate polyglutamate tissue levels in rhesus monkeys following chronic low-dose methotrexate. Cancer Drug Delivery 1987 (4):25–31
Kamen BA: Methotrexate, folate and the brain. Neurotoxicol 1986 (7):209–216
Duch DS, Lee CL, Edelstein MD, Nichol CA: Biosynthesis of tetrahydrobiopterin in the presence of dihydrofolate reductase inhibitors. Molec Pharmacol 1983 (24):103–108
Johnston MV, Silverstein FS, Greenberg M, Knutsen CA, Chandler W, Phillips T, Ensminger WD: Effects of intraventricular methotrexate on cerebrospinal fluid monoamine metabolites in rhesus monkeys. Cancer Treat Rep 1986 (70):1205–1209
Silverstein FS, Hutchinson RJ, Johnston MV: Cerebrospinal fluid biogenic amine metabolites in children during treatment for acute lymphocytic leukemia. Pediatr Res 1986 (20):285–291
Phillips PC, Thaler HT, Allen JC, Rotenberg DA: High dose leucovorin reverses acute high-dose methotrexate neurotoxicity in the rat. Ann Neurol 1989 (25):365–372
Kaminskas E, Nussey AC: Effects of methotrexate and of environmental factors on glycolysis and metabolic energy state in cultured Ehrlich ascites carcinoma cells. Cancer Res 1978 (38):2989–2996
Metha BM, Glass JP, Shapiro WR: Serum and cerebrospinal fluid distribution of 5 methyltetrahydrofolate after intravenous calcium leucovorin and intra ommaya methotrexate administation in patients with meningeal carcinomatosis. Cancer Res 1983 (43):435–538
Kufe DW, Spriggs DR: Biochemical and cellular pharmacology of cytosine arabinoside. Semin Oncol 1985 (12):34–38
Ho DHW: Distribution of kinase and deaminase of 1 D-arabinofuranosylcytosine in tissues of man and mouse. Cancer Res 1973 (33):2816–2820
Gottlieb D, Bradstock K, Kout J, Robertson T, Lee C, Castaldi P: The neurotoxicity of high dose arabinoside is age related. Cancer 1987 (60):1439–1441
Hwang TL, Yung A, Esthey EM, Fields WS: Central nervous system toxicity with high dose Ara C. Neurology 1985 (35):1475–1479
Benger A, Browman GP, Wacke IR: Clinical evidence of a cumulative effect of high dose cytarabine on the cerebellum in patients with acute leukemia. Cancer Treat Rep 1981 (61):240–241
Damon LE, Mass R, Linker CA: The association between high-dose cytarabine neurotoxicity and renal insufficiency. J Clin Oncol 1989 (7):1563–1568
Salinsky MC, Levine R, Aubuchon JP, Schutta HS: Acute cerebellar dysfunction with high dose Ara C therapy. Cancer 1983 (51):426–429
Winkelman MD, Hines JD: Cerebellar degeneration caused by the high-dose cytosine arabinoside: a clinicopathological study. Ann Neurol 1983 (14):520–527
Spector R: Pharmacokinetics and metabolism of cytosine arabinoside in the central nervous system. J Pharm Exp Ther 1982 (22):1–6
Lopez JA, Agarival RP: Acute cerebellar toxicity after high dose cytarabine associated with CNS accumulation of its metabolite uracil arabinoside. Cancer Treat Rep 1984 (68):1309–1310
Zimm S, Collins JM, Miser J, Chatteir JD, Poplack DG: Cytosine arabinoside cerebrospinal fluid kinetics. Clin Pharm Ther 1984 (35):826–830
Lopez JA, Nassif E, Vannicola P, Krikorian JG, Agarwal RP: Central nervous sytem pharmacokinetics of high dose cytosine arabinoside. J Neur Oncol 1985 (3):119–124
Band PR, Golland JF, Bernard J: Treatment of central nervous system leukemia with intrathecal cytosine arabinoside. Cancer 1973 (32):744–748
Breuer AC, Pitman SW, Dawson DM: Paraparesis following intrathecal cytosine arabinoside. Cancer 1977 (40):2817–2822
Hwang TL, Yung WKA, Lee Y, Borit A, Fields WS: High-dose Ara-C related leucoencephalopathy. J Neuro Oncol 1986 (3):335–339
Seil FJ, Leiman AC, Woodward WR: Cytosine arabinoside effects on cerebellum in tissue culture. Brain Res 1980 (186):393–408
Yamamo T, Shimada M, Abe Y, Otha S, Ohno M: Destruction of external granular layer and subsequent cerebellar abnormalities. Acta Neuropathol 1983 (59):41–47
Adlard BFP, Dobbing J, Sands J: A comparison of the effects of cytosine arabinoside and adenine arabinoside on some aspects of brain growth and development in the rat. Br J Pharmacol 1975 (54):33–39
Aguayo AL, Rome JS, Bray GM: Experimental necrosis of and arrest of proliferationof Schwann cells by cytosine arabinoside. J Neurocytol 1975 (4):663–674
Koenig H: Production of injury to feline central nervous system with nucleic acid antimetabolites. Science 1958 (127):1238–1239
Nand S, Messmore HL Jr, Patel R, Fischer SG, Fischer Rl: Neurotoxicity associated with high dose cytosine arabinoside. J Clin Oncol 1986 (4):571–575
Myers CE: The pharmacology of the fluoropyrimidines. Pharmacol Rev 1981 (33):1–15
Moertel CG, Reitemeir RJ, Bolton CF, Shorter RG: Cerebellar ataxia associated with fluorinated pyrimidine therapy. Cancer Chemother Rep 1964 (41):15–18
Lyngh HT, Droszcz CP, Albano WA, Lynch JF: Organic brain syndrome secondary to 5-fluorouracil toxicity. Dis Colon Rectum 1981 (24):130–131
Bourk E, West CR, Chheda G, Tower DB: Kinetics of entry and distribution of 5-fluorouracil in cerebrospinal fluid and brain following intravenous injection in a primate. Cancer Res 1973 (33):1735–1745
Koenig H, Patel A: Biochemical basis of the acute cerebellar syndrome in 5-fluorouracil chemotherapy. Trans Am Neurol Assoc 1969 (94):290–292
Diasia RB, Beavers TL, Carpenter JT: Familial deficiency of dihydropyrimidine dehydrogenase. J Clin Invest 1988 (81):47–51
Kuzuhara S, Ohkoshi N, Kanemarv K: Subacute leukoencephalopathy induced by carmofur, a 5-flourouracil derivative. J Neurol 1987 (234):365–370
Okeda R, Shibutani M, Matsuo T, Kuroiwa T: Subacute neurotoxicity of 5-fluorouracil and its derivative carmofur in cats. Acta Pathol Ipn 1988 (38):1255–1266
Okeda R, Karakama T, Kimura S: Neuropathologic study on chronic neurotoxicity of 5-fluorouracil and its masked compound in dog. Acta Neuropathol 1984(63):334–343
Yamamoto J, Yamashito K, Ken Ch: Effect of coadministration of uracil on the toxicity of tegafur. J Pharm Sciences 1984 (73):212–214
Kerr G, Zimm S, Collins JM, O’Neil D, Poplack DG: Effect of intravenous dose and schedule on cerebrospinal fluid. Pharmacokinetics of 5-fluorouracil in the monkey. Cancer Res 1984 (44):4929–4932
Colvin M: The alkylating agents. In: Chabner B (ed) Pharmacologic Principles of Cancer Treatment. Saunders, Philadelphia 1982 pp 276–308
Pillans PI, Ponzi SF, Parker Ml: Cyclophosphamide induced DNA strand breaks in mouse embryo cephalic tissue in vivo. Carcinogenesis 1989 (10):83–85
Colvin M: The comparative pharmacology of cyclophosphamide and ifosfamide. Semin Oncol 1982 (9):2–7
Meanwell CA, Blake AE, Kelly KA, Honigsberger L, Blackledge G: Prediction of ifosfamide/mesma associated encephalopathy. Eur J Cancer Clin Oncol 1986 (22):815–819
Goren MR, Wright RK, Pratt CB, Horowitz ME, Dodge RK, Viar JM, Kovnar EH: Potentiation of ifosfamide neurotoxicity hematotoxicity and tubular nephrotoxicity by prior cisdiamminedichloroplatinum therapy. Cancer Res 1987 (47):1457–1460
Pratt CB, Green AA, Horowitz ME, Meyer WH, Etcubanas E, Douglas E, Kovnar E: Central nervous system toxicity following the treatment of pediatric patients with ifosfamide/mesna. J Clin Oncol 1986 (4):1253–1261
Lind MJ, Margison JM, Cerny T, Thatcher N, Wilkinson PM: Comparative pharmacokinetics and alkylating activity of fractionated intravenous and oral ifosfamide in patients with bronchogenic carcinoma. Cancer Res 1989 (49):753–757
Goren MP, Wright RK, Pratt CB, Pell FE: Dechlorethylation of ifosfamide and neurotoxicity. Lancet 1986 (2):1219–1220
Osborne RJ, Slevin ML: Iphosphamide, mesna and encephalopathy. Lancet 1986 (1):601
Heim ME, Fiene R, Schick E, Wolpert E, Queiber W: Central nervous system side effects following ifosphamide monotherapy of advanced renal carcinoma. J Cancer Res Clin Oncol 1981 (100):113–116
Arndt CAS, Balis FM, Mc Cully CL, Colvin M, Poplack DG: Cerebrospinal fluid penetration of active metabolites of cyclophosphamide and ifosfamide in rhesus monkeys. Cancer Res 1988 (48):2113–2115
Cerny T, Castiglione M, Brunner K, Kupfer A, Martineli G, Lind G: Ifosfamide by continuous infusion to prevent encephalopathy. Lancet 1990 (335):175
Burger PC, Kamenar E, Schold SC, Fay JW, Phillops GL, Herzig GP: Encephalomyelopathy following high-dose BCNU therapy. Cancer 1981 (48):1318–1327
Schold SC, Fay JW: Central nervous system toxicity from high-dose treatment of systemic cancer. Neurology 1980 (30):429
Kleinschmidt-De Masters BK, Geier JM: Pathology of high-dose intraarterial BCNU. Surg Neurol 1989 (31):435–443
Mahaley MS, Whaley RA, Blue M, Bertsh L: Central neurotoxicity following intracarotid BCNU chemotherapy for malignant gliomas. J Neuro Oncol 1986 (3):297–314
Dewys WD, Fowler EH: Report of vasculitis and blindness after intracarotid injection of 1,3-bis (2 chloroethyl)-1 -nitrosurea (BCNU;NSC-409962) in dogs. Cancer Chemother Rep 1973 (57):33–40
Omojola MF, Fox AJ, Auer RN, Vinnuela FV: Hemorrhagic encephalitis produced by selective non-occlusive intracarotid BCNU injection in dogs. J Neurosurg 1982 (57)791–796
Crafts DC, Levin VA, Nielson S: Intracarotid BCNU (NSC-409962): A toxicity study in six rhesus monkeys. Cancer Treat Rep 1976 (2):541–545
Goldlewski A, Szczech J: The morphology and histochemistry of adult rat neurocytes after BCNU administration. Fol Histochem Cytobiol 1985 (23):221–230
Godlewski A: Morphological alterations in blood vessel endothelia of rat brain after administration of CCNU. Neoplasma 1986 (33):437–445
Frytak S, Shaw JN, O’Neil BP, Lee RE, Eagan RT, Shaw EG, Richardson RL, Coles DT, Jett JR: Leukoencephalopathy in small cell lung cancer patients receiving prophylactic cranial irradiation. Am J Clin Oncol 1989 (12)27–33
Gutin Ph, Weiss HD, Wiernik Ph, Wlaker MD: Intrathecal N, N’, Ntriethylenethiophosphoramide (thiotepa) in the treatment of malignant disease. Cancer 1976 (38):1471–1475
Garcia JH, Sandbank U, Gutin P: Multifocal leukoencephalopathy in adult leukemia: histologic features and etiologic considerations. Acta Neuropath 1977 (40):273–276
Strong JM, Collins JM, Lester C, Poplack DG: Pharmacokinetics of intraventricular and intravenous N, N’,Ntriethylenethiophosphoramide (thiotepa) in rhesus monkeys and humans. Cancer Res 1986 (46):6101–6104
Young RL, Ozols RF, Myers CE: The antracycline antineoplastic drugs. N Engl J Med 1981 (305):139–153
Goormaghtight E, Ruysschaert JM: Antracycline glycoside-membrane interactions. Biochim Biophys Acta 1984 (779):271–288
Merker PC, Lewis MR, Walker MD, Richardson EP Jr: Neurotoxicity of adriamycin (doxorubicin) perfusion through the cerebrospinal fluid spaces of the rhesus monkey. Toxico Appl Pharmacol 1978 (44):191–205
Siegal T, Melamed E, Sandbank V, Catane R: Early and delayed neurotoxicity of motoxantrone and doxorubicin following subarachnoid injection. J Neuro Oncol 1988 (6):135–140
Neuwelt EA, Pagel M, Barnett P, Glassbert M, Frenkel EP: Pharmacology and toxicity of intracarotid adriamycin administration following ostmotic blood brain barrier modification. Cancer Res 1981 (41):4466–4470
Cho ES, Spencer PS, Jortner BS, Schaumburg HH: A single intravenous injection of doxorubicin induces sensory neuropathy in rats. Neurotoxicol 1980 (1):583–591
Cavanagh JB, Tomiwa K, Munro PMG: Nuclear and nucleolar damage in adriamycin-induced toxicity to rat sensory ganglion cells. Neuropath Appl Neurobiol 1987 (13):23–28
Bigotte L, Olsson Y: Distribution and toxic effects of intravenously injected epirubicin on the central nervous system of the mouse. Brain 1989 (112):457–469
Hall C, Dougherty WJ, Lebish U, Brock PG, Man A: Warning against use of intrathecal mitoxantrone. Lancet 1989(1)734
Kondo A, Òhnish A, Nagara H, Tateishi J: Neurotoxicity in primary sensory neurons of adriamycin administered through retrograde axoplasmic transport in rats. Neuropathol Appl Neurobiol1987(13):177–192
England JD, Asbury AK, Rhee EK, Summer AJ: Lethal retrograde axoplasmic transport of doxorubicin to motor neurons. Brain 1988 (111):915–926
England JD, Rhee EK, Said G, Summer AJ: Schwann cell degeneration induced by doxorubicin. Brain 1988 (111):901–913
Deliconstantinos G, Kopeikina T, Siboukidou L, Villiotou V: Evaluation of membrane fluidity effects and enzyme activities alterations in adriamycin neurotoxicity. Biochemic Pharmacol 1987 (36):1153–1161
Kahman BD: Cyclosporine. N Engl J Med 1989 (321):1725–1738
Atkinson K, Boland J, Britton K, Biggs J: Blood and tissue distribution of cyclosporine in humans and in mice. Transplant Proc 1983 (1):214–217
de Groen PC, Aksamit AJ, Rakela J, Forbes GS, From RAF: Central nervous system toxicity after liver transplantation: the role of cyclosporine and cholesterol. N Engl J Med 1987 (317):861–866
Tollemar J, Ringeden O, Ericzon BG, Tyden G: Cyclosporine associated central nervous system toxicity. N Engl J Med 1988 (318):788–789
Brown Z, Neild GH: Cyclosporine inhibits prostacyclin production by cultured human endothelial cells. Transplant Proc 1987 (19):1178–1180
Thompson CB, June CH, Sullivan KM, Thomas ED: Association between cyclosporine neurotoxicity and hypomagnesaemia. Lancet 1984 (11):116–120
Bhat BD, Meriano FV, Buchwald D: Cyclosporineassociated central nervous system toxicity. N Engl J Med 1988 (318):788
Durrant S, Chipping PM, Palmer S, Gordon-Smith EC: Cyclosporin A, methylprednisolone and convulsions. Lancet 1982 (11):829–830
Davenport A, Will EJ, Davison AM, Ironside JW: Toxicity of cyclosporin metabolites. Lancet 1988 (1):333
Kunzendorf U, Brockmoller J, Jochmisen F, Keller F, Walz G, Offerman G: Cyclosporine metabolites and central nervous system toxicity. Lancet 1988 (2):1223
Adams F, Quesada JR, Gutterman JV: Neuropsychiatry manifestations of human leukocyte interferon therapy in patients with cancer. JAMA 1984 (252):938–941
Johnson DH, Hande KH, Hainsworth JD, Greco FA: Neurotoxicity of interferon. Cancer Treat Rep 1983 (67):958–961
Rohatiner AZS, Prior PF, Burton AC, Smith AT, Balkwill FR, Lister TA: Central nervous system toxicity of interferon. Br J Cancer 1983 (47):422–427
Rosenberg SA, Lotze MT, Muul LM: A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high dose interleukin-2 alone. N Engl J Med 1987 (316):889–897
Habit DV, Lipton R, Cantell K: Interferon crosses blood-brain barrier in monkey. Proc Soc Exp Biol Med 1975 (49):287–293
Salazar AM, Gibb S, Gajdusek DC, Smith RA: Clinical use of interferon: central nervous system disorders. In: Came PE, Carter NA (eds) Interferon and their applications. Berlin Heidelberg Tokyo 1984 (71) pp 471–496
Jacobs L, O’Malley, Freemand A, Murawski J, Ekes R: Intrathecal interferon in multiple sclerosis. Arch Neurol 1982 (39):609–615
Obbens E, Feun LG, Leavens ME, Savaraj N, Stewart D, Gutterman JV: Phase I clinical trial of intralesional or intraventricular leucocyte interferon for intracranial malignancies. J Neuro Oncol 1985 (3):61–67
Calvet MC, Gresser I: Interferon enhances the excitability of cultured neurones. Nature 1979 (278):558–560
Merrill JE: Effects of lymphokines and monokines on glial cells in vitro and in vivo. In: Goetzl EJ, Spector NH (eds) Physiology and Diseases. AR Liss, New York 1989 pp 89–97
Kirchner M: Interferons, a group of multiple lymphokines. Springer Semin Immunopathol 1984 (7):347–374
Lotze MT, Matory YL, Ettinghausen SE, Rayner AA, Sharrow SO, Seipp CA, Custer MC, Rosenberg SA: In vivo administration of purified interleukin-2. J Immunol 1985 (135):2865–2875
Byrne Gl, Lehmann L, Kirschbaum JG, Borden EC, Lee CM, Brown RR: Induction of tryptophan degradation in vitro and in vivo: a interferonstimulated activity. J Interf Res 1986 (6):389–396
Brown RR, Lee CM, Kohler PC, Hank JA, Storer BE, Sondel PM: Altered tryptophan and neopterin metabolism in cancer patients treated with recombinant interleukin-2. Cancer Res 1989 (49):4941–4944
Elison MD, Povlishock JT, Merchant RE: Blood brain barrier dysfunction in cats following recombinant interleukin-2 infusion. Cancer Res 1987(47):5765–5770
Lee KY, Talpaz M, Rothberg JM, Murray JL, Papadopoulos N, Plager C, Benjamin R, Levitt D, Gutterman J: Concomitant administration of recombinant human interleukin-2 and recombinant interferon-2A in cancer patients: a phase I study. J Clin Oncol 1989 (7):1726–1732
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Gangji, D., Hildebrand, J., van der Hoop, R.G. (1990). Mechanisms of Neurotoxicity and Experimental Models. In: Hildebrand, J. (eds) Neurological Adverse Reactions to Anticancer Drugs. ESO Monographs. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-76142-3_3
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