Summary
Fourty patients with malignant supratentorial gliomas received iterative intraarterial (IA) infusions of ACNU, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea at a dose of 150 mg repeated every 6 weeks. Group A consisted of eighteen patients previously treated with surgery, radiation therapy (RT) and sometimes chemotherapy, who received IA ACNU at tumor recurrence. Group B consisted of twenty two patients who received IA ACNU in the postoperative pre-RT period. In group A, 8/18 patients (44%) had an objective response, including 6/12 anaplastic astrocytomas (AA) and 2/6 glioblastoma multiforme (GBM), while 10/18 patients (56%) did not respond. Median survival time was 6 months for GBM and 12 months for AA.
In group B, 6/22 patients (27%) had an objective response (4/18 GBM and 2/4 AA) and 16/22 patients (73%) did not respond. Nine patients had such an extensive tumor after one or two courses of IA ACNU that RT was cancelled. Median survival time was 8 months for GBM and 8 months for AA.
Three patients (8%) had ophthalmologic toxicity on the infused side. There was no case of leukoencephalopathy.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Shapiro WR: Therapy of adult malignant brain tumors. What have the clinical trials taught us? Seminars in Oncology 13: 38–45, 1986
Shapiro WR, Shapiro J: Principles of brain tumors chemotherapy. Seminars in Oncology 13: 56–69, 1986
Fauchon F, Davila L, Chatellier G, Fohanno D, Philippon J, Rey A, Chiras J, Poisson M, Delattre JY: Treatment of malignant gliomas with surgery, intraarterial infusions of 1-(2-hydroxyethyl) chloroethylnitrosurea and radiation therapy. A phase II study. Neurosurg 27: 231–234, 1990
Nelson F, Nelson S, Davis R, Chu HCh, Griffin W, Pajak ThF: Survival and prognosis of patients with astrocytoma with a typical or anaplastic features. J Neuro-Oncol 3: 99–103, 1985
Fenstermacher JD, Cowles AL: Theoretic limitations of intracarotid infusions in brain tumor chemotherapy. Cancer Treat Rep 61: 519–526, 1977
Bashir R, Hochberg FH, Linggood RM, Huttleman K: Preirradiation internal carotid artery BCNU in treatment of glioblastoma multiforme. J Neurosurg 68: 917–919, 1988
Layton PB, Greenberg HS, Stetson PL, Ensminger WD, Gyves J: BCNU solubility and toxicity in the treatment of malignant astrocytomas. J Neurosurg 60: 1134–1137, 1984
Harada K, Kiya K, Uozumi T: Pharmacokinetics of a new water-soluble nitrosourea derivative (ACNU) in human gliomas. Surg Neurol 15: 410–414, 1981
Wasserman HT, Slavik M, Carter KS: Clinical comparison of the nitrosoureas. Cancer 36: 1258–1268, 1975
Nagourney AR, Fox P, Schein PS: A comparison of the biological and biochemical properties of 1-(4-amino-2-methylpirimidin-5-yl)methyl-3-(2-chloroethyl)-3-nitrosourea and 2-[3-(2-chloroethyl)-3-(nitrosoureido)]-d-glucopyranose. Cancer Res 38: 65–68, 1978
Hasegawa H, Shapiro WR, Posner JB, Basler G: Effect of 1-(4-Amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride on experimental brain tumors. Cancer Res 39: 2687–2690, 1979
Shimizu K, Ushio Y, Hayakawa T, Mogami H: Combination chemotherapy with 1-(4-Amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)3-nitrosourea hydrochloride and bleomycin in meningeal carcinomatosis in rats. Cancer Res 40: 1341–1343, 1980
Saijo N, Nishiwaki Y, Kawase I, Kobayashi T, Suzuki A, Niitani H: Effect of ACNU on primary lung cancer, mesothelioma and metastatic pulmonary tumors. Cancer Treat Rep 62: 139–141, 1978
Takakura K, AbeH, Tanaka R, Kitamura K, Miwa T, Takeuchi K, Yamamoto Sh, Kageyama N, Handa H, Mogami H, Nishimoto A, Uozumi T, Matsutani M, Nomura K: ACNU and radiotherapy for malignant glioma. J Neurosurg 64: 53–57, 1986
Burger PC, Vogel FS, Green SB, Strike ThA: Glioblastoma multiforme and 6 6 anaplastic astrocytoma. Pathologic criteria and prognostic implications. Cancer 56: 1106–1111, 1985
Yamashita J, Handa H, Tokuriki Y, Soo HY, Otsuka Sh, Suda K, Taki W: Intra-arterial ACNU therapy for malignant brain tumors. Experimental studies and preliminary clinical results. J Neurosurg 59: 424–430, 1983
Yumitori K, Handa H, Teraura T, Yamashita J: Treatment of malignant brain tumors with ACNU and phenobarbital. Acta Neurochir 70: 155–168, 1984
Papavero L, Loew F, Jaksche H: Intracarotid infusion of ACNU and 6 6 BCNU as adjuvant therapy of malignant gliomas. Clinical aspects and critical considerations. Acta Neurochir 85: 128–137, 1987
Loew F, Papavero L: The intraarterial route of drug delivery in the chemotherapy of malignant brain tumors. In: Symon L, Brihaye J, Cohadon F, Guidetti B, Loew F, Miller JD, Nornes H, Paztor E, Pertuiset B, Yasarlgil MG (eds) Advances and 6 6 Technical Standards in Neurosurgery. Springer-Verlag, Wien, 1988, pp 51–79
Rosenblum M, Delattre JY, Walker R, Shapiro W: Fatal necrotizing encephalopathy complicating treatment of malignant gliomas with intra-arterial BCNU and irradiation: A pathological study. J Neuro-Oncol 7: 269–281, 1989
Stewart J, Grahovac Z, Hugenholtz H, Russet N, Richard M, Benoit B: Combined intra-arterial and systemic chemotherapy for intracerebral tumors. Neurosurg 21: 207–213, 1987
Walker MD, Green SB, Byar DP, Alexander E, Batzdorf U, Brooks WH, Hunt WE, MacCarty CS, Mahaley SM, Meally J, Owens G, Ransohoff J, Robertson JT, Shapiro WR, Smith KR, Wilson ChB, StrikeTh: Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. New Engl J Med 303: 1323–1329, 1980
Walker MD, Alexander E, Hunt WE, MacCarty CS, Mahaley SM, Mealey J, Norhell HA, Owens G, Ransohoff J, Wilson ChB, Gefan E, Strike Th: Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg 49: 333–343, 1978
Hochberg FH, Pruitt AA, Beck DO, DeBrun G, Davis K: The rationale and 6 6 methodology for intra-arterial chemotherapy with BCNU as treatment for glioblastoma. J Neurosurg 63: 876–880, 1985
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Vega, F., Davila, L., Chatellier, G. et al. Treatment of malignant gliomas with surgery, intraarterial chemotherapy with ACNU and radiation therapy. J Neuro-Oncol 13, 131–135 (1992). https://doi.org/10.1007/BF00172762
Issue Date:
DOI: https://doi.org/10.1007/BF00172762