Summary
Central neurotoxicity is reported in 5 of 16 patients with recently diagnosed anaplastic gliomas, who received intra-arterial BCNU (200 mg/M2/course) and also 2 in a series of 26 patients with recurrent gliomas similarly treated. Neurotoxicity was usually delayed, commencing several weeks following the second or third course. CT scans during central neurotoxicity represented 1 or more of 3 patterns: no change; increased low density area(s); and/or ipsilateral gyral enhancement and punctate calcification in the middle cerebral artery territory. In one clinicopathological correlation, coagulative necrosis of the white matter was observed, identical histologically to those changes recognized as delayed vascular events following radiotherapy. Cautious exploration of the various clinical factors that may contribute to this toxicity seems appropriate, as exploration of the potential benefits of regional chemotherapeutic infusions is undertaken.
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Walker MD, Alexander E Jr, Hunt WE, MacCarty CS, Mahaley MS Jr, Mealey J Jr, Norrell HA, Owens G, Ransohoff J, Wilson CB, Gehan EA, Strike TA: Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg 49:333–343, 1978.
Greenberg HS, Ensminger WD, Chandler WF, Layton PB, Junck L, Knake J, Vine AK: Intra-arterial BCNU chemotherapy for treatment of malignant gliomas of the central nervous system. J Neurosurg 61:423–429, 1984.
Grimson BS, Mahaley MS Jr, Dubey HD, Dudka L: Ophthalmic and central nervous system complications following intracarotid BCNU (Carmustine). J Clin Neuroophthalmol 1:261–264, 1981.
Kapp J, Vance R, Parker JL, Smith RR: Limitations of high dose intra-arterial 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) chemotherapy for malignant gliomas. Neurosurgery 10(6):715–719, 1982.
Phillips TW, Chandler WIT, Kindt GW, Ensminger WD, Greenberg HS, Seeger JF, Doan KM, Gyves JW: New implantable continuous administration and bolus dose intracarotid drug delivery system for the treatment of malignant gliomas. Neurosurgery 11:213–218, 1982.
Stewart DJ, Wallace S, Feun L, Leavens M, Young SE, Handel S, Mavligit G, Benjamin RS: A phase I study of intracarotid artery infusion of cisdiamminedichloroplatinum (II) in patients with recurrent malignant intracerebral tumors. Cancer Res 42:2059–2062, 1982.
West CR, Avellanosa AM, Barua NR, Patel A, Hong CI: Intraarterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and systemic chemotherapy for malignant gliomas: A follow-up study. Neurosurgery 13:420–426, 1983.
Stewart DJ, Grahovac Z, Benoit B, Addison D, Richard MT, Dennery J, Hugenholtz H, Russell N, Peterson E, Maroun JA, Vandenberg T, Hopkins HS: Intracarotid chemotherapy with a combination of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cis-Diaminedichloroplatinum (Cis-platin), and 4′-0-Demethyl-1-O(4,6-O-2-thenylidene-D-glucopyranosyl)epipodophyllotoxin (VM-26) in the treatment of primary and metastatic brain tumors. Neurosurgery 15:828–833, 1984.
Aronin PA, Mahaley MS Jr, Rudnick SA, Dudka L, Donohue JF, Selker RG, Moore P: Prediction of BCNU pulmonary toxicity in patients with malignant gliomas. N Eng J Med 303:183–188, 1980.
Woodhall B, Hall K, Mahaley S Jr, Jackson J: Chemotherapy of brain cancer: Experimental and clinical studies in localized hypothermic cerebral perfusion. Ann Surg 150:640–652, 1959.
Woodhall B, Mahaley MS Jr: Isolated perfusion in treatment of advanced carcinoma. Am J Surg 105:624–627, 1963.
Eckman WW, Patlak CS, Fenstermacher JD: A critical evaluation of the principles governing the advantages of intra-arterial infusions. J Pharmacokinet Biopharmacokinet 2:257–285, 1974.
Debrun GM, Davis KR, Hochberg FH: Superselective injection of BCNU through a latex calibrated-leak balloon. AJNR 4:399–400, 1983.
Layton PB, Greenberg HS, Stetson PL, Ensminger WD, Gyves JW: BCNU solubility and toxicity in the treatment of malignant astrocytomas. J Neurosurg 60:1134–1137, 1984.
Bullard D: Personal communication.
DeWys WD, Fowler EH: Report of vasculitis and blindness after intracarotid injection of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU; NSC-409962) in dogs. Cancer Chemo Rep 57:33–40, 1973.
Omojola MF, Fox AJ, Auer RN: Hemorrhagic encephalitis produced by selective non-occlusive intracarotid BCNU injection in dogs. J Neurosurg 57:791–796, 1982.
Popovic P, Popovic V, Weathers DR: BCNU toxicity in rats: hematologic and histologic studies. Abstract, International Symposium on Multidisciplinary Aspects of Brain Tumor Therapy, Los Angeles, California, 1979, pp 136–137.
Walker MD, Green SB, Byar DP, Alexander E Jr, Batzdorf U, Brooks WH, Hunt WE, MacCarty CS, Mahaley MS Jr, Mealey J Jr, Owens G, Ransohoff J II, Robertson JT, Shapiro WR, Smith KR Jr, Wilson CB, Strike TA: Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Eng J Med 303:1323–1329, 1980.
Safdari H et al. Personal communication.
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Mahaley, M., Whaley, R.A., Blue, M. et al. Central neurotoxicity following intracarotid BCNU chemotherapy for malignant gliomas. J Neuro-Oncol 3, 297–314 (1986). https://doi.org/10.1007/BF00165578
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DOI: https://doi.org/10.1007/BF00165578