Abstract
The treatment of central nervous system malignancy represents one of the single greatest challenges in the field of cancer medicine. The great strides in the treatment of extracerebral malignancy achieved in the past two decades have not been accompanied by an appreciable improvement in the treatment of intracerebral malignancies, either primary or metastatic. Now that effective therapy is available for acute lymphocytic leukemia, brain tumors are emerging as the most common cause of nonaccidental death in children over 6 months of age. In adults, malignant glioma, the most common brain tumor, remains a lethal disease in almost all of affected individuals. Also, the number of patients with central nervous system metastases from systemic cancer continues to increase (Table 1), mainly because the risk of central nervous system infiltration in such patients appears to be directly proportional to the duration of survival. As survival has increased, so has the incidence of central nervous system metastases. Ironically, success in the treatment of systemic malignancy has created a new problem, one that underscores the need for more effective therapy for central nervous system neoplasia.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Abelson, H. T., Ensminger, W. D., Rosowsky, A.: Serum and cerebrospinal fluid pharmacokinetic studies of high dose methotrexate-carboxypeptidase G. Proc. Am. Assoc. Cancer Res.20:213, 1979.
Abelson, H. T., Ensminger, W., Rosowsky, A., Uren, J.: Comparative effects of citrovorum factor and carboxypeptidase G on cerebrospinal fluid-methotrexate pharmacokinetics. Cancer Treatment Rep.62:1549–1552, 1978.
Allen, J. C., Hasegawa, H., Mehta, B., Shapiro, W. R., Posner, J. B.: CNS penetration of methotrexate is enhanced by hyperosmolar intracarotid mannitol and meningeal carconimatosis. Neurology28:351, 1978.
Allen, J. C., Hasegawa, H., Mehta, B. M., Shapiro, W. R., Posner, J. B.: Influence of intracarotid mannitol on intracerebral methotrexate concentrations surrounding experimental brain tumors. Proc. Am. Assoc. Cancer Res.20:286, 1979.
Anton, A. H., Solomon, H. M.: Drug-protein binding. Ann. N. Y. Acad. Sci.226:1–362, 1973.
Aur, R. J. A., Simone, J., Hustur, H. P., Walters, T., Borella, L., Pratt, C., Pinkel, D.: Central nervous system therapy and combination chemotherapy of childhood lymphocytic leukemia. Blood37:272–281, 1971.
Benson, D. F., LeMay, M., Patten, D. H., Rubeno, A. B.: Diagnosis of normal pressure hydrocephalus. N. Engl. J. Med.283:609–615, 1970.
Bering, E. A., Rall, D. P., Walker, M., Leventhal, C., Ommaya, A.: Intrathecal chemotherapy of gliomas: Rationale and current status. Ann. N. Y. Acad. Sci.159:599–602, 1969.
Blasberg, R. G.: Methotrexate, cytosine arabinoside and BCNU concentration in brain after ventriculocisternal perfusion. Cancer Treatment Rep.61:625–631, 1977.
Blasberg, R. G.: Pharmacodynamics and the blood-brain barrier. In Modern Concepts in Brain Tumor Therapy: Laboratory and Clinical Investigations. Natl. Cancer Inst. Monogr.46:19–27, 1977.
Blasberg, R. G.: Pharmacokinetics and metastatic brain tumor chemotherapy. In Weiss, L., Gilbert, H., and Posner, J. (eds.): Brain Metastases. Boston, G. K. Hall and Company, 1980.
Blasberg, R. G., Patlak, C., Fenstermacher, J. D.: Intrathecal chemotherapy: Brain tissue profiles after ventricular perfusion. J. Pharmacol. Exp. Ther.195:73–83, 1975.
Blasberg, R. G., Patlak, C. S., Shapiro, W. R.: Distribution of methotrexate in the cerebrospinal fluid and brain after intraventricular administration. Cancer Treatment Rep.61:633–641, 1977.
Bleyer, W. A., Poplack, D. G.: Clinical studies on the central-nervous-system pharmacology of methotrexate. In Pinedo, H. M. (ed.): Clinical Pharmacology of Antineoplastic Drugs. Amsterdam, Elsevier/North-Holland, 1978, pp. 115–131.
Bleyer, W. A., Poplack, D. G.: Intraventricular vs. intralumbar methotrexate for central nervous system leukemia: Prolonged remission with the Ommaya reservoir. Med. Pediatr. Oncol.6:207–213, 1979.
Bleyer, W. A., Poplack, D. G., Simon, R. M.: “Concentration × time” methotrexate via a subcutaneous reservoir: A less toxic regimen for intraventricular chemotherapy of central nervous system neoplasms. Blood51:835–842, 1978.
Bleyer, W. A., Savitch, J. L., Hartmann, J. R.: Is aminopterin a safer drug for intrathecal injection than methotrexate? Proc. Am. Assoc. Cancer Res.20:179, 1979.
Bleyer, W. A., Savitch, J., Poplack, D. G.: Methotrexate in cerebrospinal fluid. N. Engl. J. Med.293:1152, 1975.
Bode, U., Magrath, I., Bleyer, W., Poplack, D., Glaubiger, D.: Mechanism for methotrexate efflux from the cerebrospinal fluid in man. Proc. Am. Assoc. Clin. Oncol.20:375, 1979.
Brightman, M. W., Reese, T. S., Vick, N. A., Bigner, D. D.: A mechanism underlying the lack of a blood-brain barrier to peroxidase in virally induced brain tumors. J. Neuropathol. Exp. Neurol.30:139–140, 1971.
Bruckner, H. W., Cohen, C. J., Kabakow, B., Wallach, R. C., Greenspan, E. M., Gusberg, S. B., Holland, J. F.: Combination chemotherapy of ovarian carcinoma with platinum: Improved therapeutic index. Proc. Am. Assoc. Cancer Res.18:339, 1977.
Bunn, P., Schein, P.: Meningeal involvement in lymphoma. N. Engl. J. Med.290:517, 1974.
Capizzi, R. L., DeConti, R. C., Marsh, J. C. Bertino, J. R.: Methotrexate therapy of head and neck cancer: Improvement in therapeutic index by use of leucovorin “rescue.” Cancer Res.30:1782–1788, 1970.
Catane, R., Kaufman, J., West, C., Merrin, C., Tsukada, Y., Murphy, G. P.: Brain metastasis from prostatic carcinoma. Cancer38:2583–2587, 1976.
Clemente, C. D., Holst, E. A.: Pathological changes in neurons, neuroglia and blood-brain barrier induced by X-irradiation of heads of monkeys. Arch. Neurol. Psychiatry71:66–79, 1954.
Cowles, A. L., Fenstermacher, J. D.: Theoretical considerations in the chemotherapy of brain tumors. In Sartorelli, A. C., Johns, D. G. (eds.): Handbook of Experimental Pharmacology, Vol. 38. Berlin and New York, Springer-Verlag, 1979, pp. 319–329.
Cox, J. D., Petrovich, Z., Paig, C., Stanley, K.: Prophylactic cranial irradiation in patients with inoperable carcinoma of the lung. Cancer42:1135–1140, 1978.
Currie, S., Henson, R. A.: Neurological syndromes in the reticuloses. Brain94:307–320, 1971.
Dawson, D. M., Rosenthal, D. S., Moloney, W. C.: Neurological complications of acute leukemia in adults: Changing rate. Ann. Intern Med.79:541–544, 1973.
Dawson, H.: A comparative study of the aqueous humor and cerebrospinal fluid in the rabbit. J. physiol.129:111–133, 1955.
DiChiro, G., Hammock, M. K., Bleyer, W. A.: Spinal descent of cerebrospinal fluid in man. Neurology26:1–8, 1976.
Fleming, I., Simone, J., Jackson, R., Johnson, W., Walters, T., Mason, C.: Splenectomy and chemotherapy in acute myelocytic leukemia of childhood. Cancer33:427–434, 1974.
Frey, A. H., Feld, S. R., Frey, S.: Neural function and behavior: Defining the relationship. Ann. N. Y. Acad. Sci.247:433–439, 1975.
Fyfe, M. J., Goldman, I. D.: Characteristics of vincristine induced augmentation of methotrexate uptake in Ehrlich ascites tumor cells. J. Biol. Chem.248:5067–5073, 1973.
Gerovich, F. G., Luna, M. A., Gottlieb, J. A.: Increased indicence of cerebral metastases in sarcoma patients with prolonged survival from chemotherapy. Cancer36:1843–1851, 1975.
Goldman, I. D.: Effects of methotrexate on cellular metabolism: Some critical elements in the drug-cell interaction. Cancer Treatment Rep.61:549–558, 1977.
Gormley, P., Poplack, D., Pizzo, P.: The cerebrospinal fluid pharmacokinetics of cis-diamminedichloroplatinum (II) and several platinum analogues. Proc. Am. Assoc. Cancer Res.20:1131, 1979.
Griffin, T. W., Rasey, J. S., Bleyer, W. A.: The effect of photon irradiation in blood-brain barrier permeability to methotrexate in mice. Cancer40:1109–1111, 1977.
Griffin, J. W., Thompson, R. W., Mitchinson, M. J.: Lymphomatous leptomeningitis. Am. J. Med.51:200–208, 1971.
Ho, D. H. W., Frei, E., III: Clinical pharmacology of 1-ß-D-arabinofuranosylcytosine. Clin. Pharmacol. Ther.12:944–954, 1971.
Hoshino, T.: Therapeutic implications of brain tumor cell kinetics. In Modern Concepts in Brain Tumor Therapy: Laboratory and Clinical Investigations. Natl. Cancer Inst. Monogr.46:171–178, 1977.
Hoshino, T., Barker, M., Wilson, C. B., Boldrey, E. B., Fewer, D.: Cell kinetics of human gliomas. J. Neurosurg.37:15–26, 1972.
Huffman, D. H., Wan, S. H., Azarnoff, D. L., Hoogstraten, B.: Pharmacokinetics of methotrexate. Clin. Pharmacol. Ther.14:572–579, 1973.
Kay, H. E. M.: Development of CNS leukemia in acute myeloid leukemia in childhood. Arch. Dis. Child.51:73–74, 1976.
Kieffer, S. A., Wolff, J. M., Prentice, W. B., Loken, M. K.: Scinticisternography in individuals without known neurological disease. Am. J. Roentgenol.112:225–239, 1971.
Koch-Wesser, J., Sellers, E. M.: Drug therapy: Binding of drugs to serum albumin. N. Engl. J. Med. 294:311–316, 1976.
Kury, G., Carter, H. D.: Autoradiographic study of human nervous system tumors. Arch. Pathol.80:38–42, 1965.
Law, I. P., Blom, J.: Adult acute leukemia: Frequency of central nervous system involvement in long term survivors. Cancer40:1304–1306, 1977.
Levin, V. A., Freeman-Dove, M., Dandahl, H. D.: Permeability characteristics of brain adjacent to tumors in rats. Arch. Neurol.32:785–791, 1975.
Levin, V. A., Landahl, H. D., Freeman-Dove, M. A.: The application of brain capillary permeability coefficient measurements to pathological conditions and the selection of agents which cross the blood-brain barrier. J. Pharmacokinet. Biopharm.4:499–519, 1976.
Mayer, S., Maickel, R. P., Brodie, B. B.: Kinetics of penetration of drugs and other foreign compounds into cerebrospinal fluid and brain. J. Pharmacol.127:205–211, 1959.
Mehta, Y., Hendrickson, F. R.: CNS involvement in Ewing’s sarcoma. Cancer33:859–862, 1974.
Mellet, L. B.: Physiochemical considerations and pharmacokinetic behavior in delivery of drugs to the central nervous system. Cancer Treatment Rep.61:527–531, 1977.
Nair, V., Roth, L. J.: Effect of x-irradiation and certain other treatments in blood-brain barrier permeability. Radiat. Res.23:249–264, 1964.
Nystrom, S.: Pathological changes in blood vessels of human glioblastoma multiforme: Comparative studies using plastic casings, angiography, light microscopy, and with references to some other brain tumors. Acta Pathol. Microbiol. Scand., Suppl. 137, 1960.
Ommaya, A. K.: Immunotherapy of gliomas: a review. Adv. Neurol.15:337–359, 1976.
Ommaya, A. K.: Subcutaneous reservoir and pump for sterile access to ventricular cerebrospinal fluid. Lancet2:983–984, 1963.
Oscar, K. J., Hawkins, T. D.: Microwave alteration of the blood-brain barrier system of rats. Brain Res.126:281–293, 1977.
Pizzo, P. A., Poplack, D. G., Bleyer, W. A.: The neurotoxicities of current leukemia therapy. Am. J. Pediat. Hematol. Oncol.1:127–140, 1979.
Poplack, D. G., Bleyer, W. A., Wood, J. H.: A primate model for the study of the CNS pharmacokinetics of antineoplastic agents. In Whitehouse, J. M. (ed.): CNS Complications of Malignant Disease. Hampshire, England, Macmillan Press, 1979, pp. 395–404.
Rapoport, S. I., Hori, M., Klatzo, I.: Testing of a hypothesis for osmotic opening of the blood-brain barrier. Am. J. Physiol.223:323–331, 1972.
Rapoport, S. I., Ohno, K., Fredericks, W. R., Pettigrew, K. D.: Regional cerebrovascular permeability to 14C sucrose after osmotic opening of the blood-brain barrier. Brain Res.150:653–657, 1978.
Sansone, G.: Pathomorphosis of acute infantile leukemia treated with modern therapeutic agents; “meningoleukemia” and Frohlich obesity. Ann. Paediatr.183:33, 1954.
Schettler, T., Shealy, C. N.: Experimental selective alteration of blood-brain barrier by X-irradiation. J. Neurosurg.32:89–94, 1970.
Shapiro, W. R., Posner, J. B., Ushio, Y., Chernik, N. L., Young, D. F.: Treatment of meningeal neoplasms. Cancer Treatment Rep.61:733–743, 1977.
Shapiro, W. R., Young, D. F., Mehta, B. M.: Methotrexate: Distribution in cerebrospinal fluid after intravenous ventricular and lumbar injections. N. Engl. J. Med.293:161–166, 1975.
Shealy, C. N., Crafts, D.: Selective alteration of the blood-brain barrier. J. Neurosurg.23:484–487, 1955.
Tefft, M., Fernandez, C., Donaldson, M., Newton, W., Moon, T. E.: Incidence of meningeal involvement by rhabdomyosarcoma of the head and neck in children. Cancer42:253–258, 1978.
Tejada, F., Zubrod, C. G.: Vincristine effect on methotrexate cerebrospinal fluid concentration. Cancer Treatment Rep.63:143–145, 1979.
Van Dilla, M. A., Trujillo, T. T., Mullaney, P. E., Coulter, J. R.: Cell microfluorometry: A method for rapid fluorescence measurement. Science163:1213–1214, 1969.
Vick, N. A., Bigner, D. D.: Microvascular abnormalities in virally-induced canine brain tumors: Structural basis for altered blood-brain barrier function. J. Neurol. Sci.17:29–39, 1972.
Vick, N. A., Khandekar, J. D., Bigner, D. D.: Chemotherapy of brain tumors: The “blood-brain barrier” is not a factor. Arch. Neurol.34:523–526, 1977.
Weiss, H. D., Walker, M. D., Wiernik, P. H.: Neurotoxicity of commonly used antineoplastic agents. N. Engl. J. Med.291:75–81, 127-233, 1974.
Wolk, R. W., Masse, S. R., Conklin, R., Freireich, E. J.: The incidence of central nervous system leukemia in adults with acute leukemia. Cancer33:863–869, 1974.
Yap, H. Y., Yap, B. S., Tashiwa, C. K., DiStefano, A., Blumenschein, G. R.: Meningeal carcinomatosis in breast cancer. Cancer42:283–286, 1978.
Zaharko, D. S.: Pharmacokinetics and drug effect. Biochem. Pharmacol.23(suppl. 2):1–8, 1974.
Ziegler, J. L., Bluming, A. Z., Morrow, R. M., Fass, L., Carbone, P. P.: Central nervous system involvement in Burkitt’s lymphoma. Blood36:718–728, 1970.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1980 Plenum Press, New York
About this chapter
Cite this chapter
Poplack, D.G., Horowitz, M.E., Bleyer, W.A. (1980). Pharmacology of Antineoplastic Agents in Cerebrospinal Fluid. In: Wood, J.H. (eds) Neurobiology of Cerebrospinal Fluid 1. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-1039-6_39
Download citation
DOI: https://doi.org/10.1007/978-1-4684-1039-6_39
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-1041-9
Online ISBN: 978-1-4684-1039-6
eBook Packages: Springer Book Archive