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Current Options for the Treatment of Neoplastic Meningitis

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Abstract

Neoplastic meningitis, which is the diffuse involvement of the leptomeninges by infiltrating cancer cells, may be caused by many systemic tumors. The treatment options for neoplastic meningitis disease remain unsatisfactory. In this review article, we discuss the pathogenesis and cytology of neoplastic meningitis and the options for treatment, including intrathecal chemotherapy, systemic chemotherapy, and newer agents such as cytokines and monoclonal antibodies.

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References

  1. Posner JB, Chernik NL: Intracranial metastasis from systemic cancer. Adv Neurol 19: 579–592, 1978

    Google Scholar 

  2. Bleyer WA: Leptomeningeal cancer in leukemia and solid tumors. Curr Probl Cancer 12: 185–237, 1988

    Google Scholar 

  3. Liaw C, Ng K, Huang JS, Wang CH, Kiu MC, Lai GM: Meningeal carcinomatosis from solid tumours: Clinical analysis of 42 cases. J Formosan Med Assoc 91: 299–303, 1992

    Google Scholar 

  4. Klein P, Haley EC, Wooten GF, VandenBerg SR: Focal cerebral infarctions associated with perivascular tumor infiltrates in carcinomatous leptomeningeal metastases. Arch Neurol 46: 149–152, 1989

    Google Scholar 

  5. Balducci L, Little DD, Khansur T, Steinberg MH: Carcinomatous meningitis in small cell lung cancer. Am J Med 267: 31–33, 1984

    Google Scholar 

  6. Brucher JM, Cervos-Navarro J: La carcinomatose meninge etude anatomiquede 11 cas. Acta Neurolog Psychiatr Belgica 60: 368, 1960

    Google Scholar 

  7. Kirkwood JM, Bankole DO: Carcinomatous meningitis at Yale 1970–1980. Proc Am Assoc Cancer Res 22: 342, 1981

    Google Scholar 

  8. Amer MH, Al-Sarraf M, Baker LH, Vaitkevicius VK: Malignant melanoma and central nervous system metastases: incidence, diagnosis, treatment and survival. Cancer 42: 660–668, 1978

    Google Scholar 

  9. Stanley P, Senac MO Jr, Segall HD: Intraspinal seeding from intracranial tumors in children. AJR Am J Roentgenol 144(1): 157–161, 1984

    Google Scholar 

  10. Packer RJ, Siegel KR, Sutton LN, Litmann P, Bruce DA, Schut L: Leptomeningeal dissemination of primary central nervous system tumors of childhood. Ann Neurol 18: 217–221, 1985

    Google Scholar 

  11. Morganroth J, Deisseroth A, Winokur S, Schein P: Differentiation of carcinomatous and bacterial meningitis. Neurology 22: 1240–1242, 1972

    Google Scholar 

  12. Price RA, Johnson WW: The central nervous system in childhood leukemia. Cancer 27: 247, 1971

    Google Scholar 

  13. Gonzalez-Vitale JC, Garcia-Bunuel R: Meningeal carcinomatosis. Cancer 27: 2906–2911, 1976

    Google Scholar 

  14. Gamache FW, Posner JB, Patterson RH: Metastatic brain tumors: leptomeningeal metastases. In: Youmans JR (ed) Neurological Surgery. Vol 5. Saunders, Philadelphia 182: 2888–2895, 1989

    Google Scholar 

  15. Zachariah B, Zachariah SB, Varghese R, Balducci L: Carcinomatous meningitis: clinical manifestations and management. Int J Clin Pharmacol Ther 33: 7–12, 1995

    Google Scholar 

  16. Sze G, Soletsky S, Bronen R, Krol G: MR imaging of the cranial meninges with emphasis on contrast enhancement and meningeal carcinomatosis. Am J Nucl Radiol 10: 965–975, 1989

    Google Scholar 

  17. Little JR, Dale AJD, Okazaki H: Meningeal carcinomatosis. Arch Neurol 30: 122–137, 1974

    Google Scholar 

  18. Olson ME, Chernik NL, Posner JB: Infiltration of leptomeninges by systemic cancer. Arch Neurol 30: 122–137, 1974

    Google Scholar 

  19. Wasserstrom WR, Glass JP, Posner JB: Diagnosis and treatment of leptomeningeal metastasis from solid tumours: Experience with 90 patients. Cancer 49: 759–772, 1982

    Google Scholar 

  20. Freilich RJ, Krol G, DeAngelis LM: Neuroimaging and cerebrospinal fluid cytology in the diagnosis of leptomeningeal metastasis. Ann Neurol 38: 51–57, 1995

    Google Scholar 

  21. Chamberlain MC: Current concepts in leptomeningeal metastasis. Curr Opin Oncol 4: 533–539, 1992

    Google Scholar 

  22. Moseley RP, Oge K, Shafquat S, Moseley CM, Sullivan NM, Badley RA, Burchell J, Taylor-Papadimitriou J, Coakham HB: HMFGI antigen: a new marker for carcinomatous meningitis. Int J Cancer 44: 440–444, 1989

    Google Scholar 

  23. Lampl Y, Paniri Y, Eshel Y, Sarova-Pinchas I: Alkaline phosphatase level in CSF in various brain tumours and pulmonary carcinomatous meningitis. J Neuro-Oncol 9: 35–40, 1990

    Google Scholar 

  24. Siegal T, Ovadia H, Yatsiv I, Abramsky O: CSF myelin basic protein levels in leptomeningeal metastases. Relationship to disease activity. J Neurol Sci 78: 165–173, 1987

    Google Scholar 

  25. Weller M, Sommer N, Stevens A, Wietholter H: Increased intrathecal synthesis of fibronectin in bacterial and carcinomatous meningitis. Acta Neurol Scand 82: 138–142, 1990

    Google Scholar 

  26. DeAngelis LM: Current diagnosis and treatment of leptomeningeal metastasis. J Neuro-Oncol 38: 245–252, 1998

    Google Scholar 

  27. Blaney SM, Balis FM, Poplack DG: Pharmacologic approaches to the treatment of meningeal malignancy. Oncology 5: 107–116, 1991

    Google Scholar 

  28. Lishner M, Perrin RG, Feld R, Messner HA, Tuffnell PG, Elhakim T, Matlow A, Curtis JE: Complications associated with Ommaya reservoirs in patients with cancer. Arch Int Med 150: 173–176, 1990

    Google Scholar 

  29. Shapiro WR, Posner JB, Ushio Y, Chemik NL, Young DF: Treatment of meningeal neoplasms. Cancer Treat Rep 61: 733–743, 1977

    Google Scholar 

  30. Jayson GC, Howell A, Harris M, Morgenstern G, Chang J, Ryder WD: Carcinomatous meningitis in breast cancer: An aggressive disease variant. Cancer 74: 3155–3141, 1994

    Google Scholar 

  31. Shapiro WR, Young DF, Mehta BM: Methotrexate distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. New Engl J Med 293: 161–166, 1975

    Google Scholar 

  32. Petit T, Dufour P, Korganov AS, Maloise F, Oberling F: Continuous intrathecal perfusion of methotrexate for carcinomatous meningitis with pharmacokinetic studies: Two case studies. Clin Oncol 9: 189–190, 1997

    Google Scholar 

  33. Ongerboer de Visser BW, Somers R, Nooyen WH, Van Heerde P, Hart AA, McVie JG: Intraventricular methotrexate therapy of leptomeningeal metastasis from breast cancer. Neurology 33: 1565–1572, 1983

    Google Scholar 

  34. Boogerd W, Hart AAM, Van der Sande JJ, Engelsman E: Meningeal carcinomatosis in breast cancer. Prognostic factors and influence of treatment. Cancer 67: 1685–1695, 1991

    Google Scholar 

  35. Hitchins RN, Bell DR, Woods RL, Levi JA: A prospective randomized trial of single-agent versus combination chemotherapy in meningeal carcinomatosis. J Clin Oncol 5: 1655–1662, 1987

    Google Scholar 

  36. Sculier JP: Treatment of meningeal carcinomatosis. Cancer Treat Rev 12: 95–104, 1985

    Google Scholar 

  37. Boogerd W, Van der Sande JJ, Moffie D: Acute fever and delayed leukoencephalopathy following low dose intraventricular methotrexate. J Neurol Neurosurg Psychiatr 51: 1277–1283, 1988

    Google Scholar 

  38. Gutin PH, Weiss HD, Wiernik PH, Walker MD: Intrathecal N,N',N''-triethylenethiophosphoramide [thio-TEPA (NSC 6396)] in the treatment of malignant meningeal disease. Cancer 38: 1471–1475, 1976

    Google Scholar 

  39. Gutin PH, Levi JA, Wiernik PH, Walker MD: Treatment of malignant meningeal disease with intrathecal thioTEPA: A phase II study. Cancer Treat Rep 61: 885–887, 1977

    Google Scholar 

  40. Fulton DS, Levin VA, Gutin PH, Edwards MS, Seager ML, Stewart J, Wilson CB: Intrathecal cytosine arabinoside for the treatment of meningeal metastases from malignant brain tumors and systemic tumors. Cancer Chemother Pharmacol 8: 285–291, 1982

    Google Scholar 

  41. Grossman SA, Finkelstein DM, Ruckdeschel JC, Trump DL, Moynihan T, Ettinger DS: Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. J Clin Oncol 3: 561–569, 1993

    Google Scholar 

  42. Chamberlain MC: Pediatric leptomeningeal metastases: outcome following combined therapy. J Child Neurol 12: 53–59, 1997

    Google Scholar 

  43. Wasserstrom WR, Glass JP, Posner JB: Diagnosis and treatment of leptomeningeal metastases from solid tumors: Experience with 90 patients. Cancer 49: 759–772, 1982

    Google Scholar 

  44. Mellett L: Physiochemical consideration and pharmacokinetic behavior in delivery of drugs to the central nervous system. Cancer Treat Rep 61: 527–531, 1977

    Google Scholar 

  45. Slevin ML, Piall EM, Aherne GW, Harvey VJ, Johnston A, Lister TA: Effect of dose and schedule on pharmacokinetics of high-dose cytosine arabinoside on plasma and cerebrospinal fluid. J Clin Oncol 9: 546–551, 1983

    Google Scholar 

  46. Postmus PE, Haaxma-Reiche H, Berendsen HH, Sleijfer DT: High dose etoposide for meningeal carcinomatosis in patients with small cell lung cancer. Eur J Cancer Clin Oncol 25: 377–378, 1989

    Google Scholar 

  47. McCowage G, Tien R, McLendon R, Felsberg G, Fuchs H, Graham ML, Kurtzberg J, Moghrabi A, Ferrell L, Kerby T, Duncan-Brown M, Stewart E, Robertson PL, Colvin OM, Golembe B, Bigner DD, Friedman HS: Successful treatment of childhood pilocytic astrocytomas metastatic to the leptomeninges with high-dose cyclophosphamide. Med Pediatr Oncol 27: 32–39, 1996

    Google Scholar 

  48. Tallal L, Tan C, Oettgen H, Wollner N, McCarthy M, Helson L, Burchenal J, Karnofsky D, Murphy ML: E. coli L-asparaginase in the treatment of leukemia and solid tumors in 131 children. Cancer 25: 306–320, 1970

    Google Scholar 

  49. Siegal T: Leptomeningeal metastases: Rationale for systemic chemotherapy or what is the role of intra-CSF-chemotherapy. J Neuro-Oncol 38: 151–157, 1998

    Google Scholar 

  50. Siegal T, Lossos A, Pffefer M: Leptomeningeal metastases: Analysis of 31 patients with sustained off-therapy response following combined-modality therapy. Neurology 44: 1463–1469, 1994

    Google Scholar 

  51. Theodore WH, Gendelman S: Meningeal carcinomatosis. Arch Neurol 38: 696–699, 1981

    Google Scholar 

  52. Giannone L, Greco FA, Hainsworth JD: Combination intraventricular chemotherapy for meningeal neoplasia. J Clin Oncol 4: 68–73, 1986

    Google Scholar 

  53. Nakagawa H, Fujita T, Kubo S, Tzumoto S, Nakajima Y, Tsuruzono K, Tokiyoshi K, Hayakawa T: Ventriculolumbar perfusion chemotherapy with methotrexate and cytosine arabinoside for meningeal carcinomatosis: A pilot study in 13 patients. Surg Neurol 45: 256–264, 1996

    Google Scholar 

  54. Chamberlain MC, Kormanik PA: Prognostic significance of coexistent bulky metastatic central nervous system disease in patients with leptomeningeal metastases. Arch Neurol 54: 1364–1368, 1997

    Google Scholar 

  55. Chatelut E, Kim T, Kim S: A slow-release methotrexate formulation for intrathecal chemotherapy. Cancer Chemother Pharmacol 32: 179–182, 1993

    Google Scholar 

  56. Kim S, Chatelut E, Kim JC, Howell SB, Cates C, Kormanik PA, Chamberlain MC: Extended CSF cytarabine 88 exposure following intrathecal administration of DTC 101. J Clin Oncol 11: 2186–2193, 1993

    Google Scholar 

  57. The Cancer Letter 24, No. 45, November 27, 1998

  58. Berg SL, Balis FM, Zimm S, Murphy RF, Holcenberg J, Sato J, Reaman G, Steinherz P, Gillespie A, Doherty K: Phase I/II trial and pharmacokinetics of intrathecal diaziquone in refractory meningeal malignancies. J Clin Oncol 10: 143–148, 1992

    Google Scholar 

  59. Blaney S, Balis F, Murphy R, Arndt C, Gillespie A, Poplack D: A phase I study of intrathecal mafosfamide (MF) in patients with refractory meningeal malignancies. (Abstract 274 ). Proc Am Soc Clin Oncol 11: 113, 1992

    Google Scholar 

  60. Adamson PC, Balis FM, Arndt CA, Holcenberg JS, Narang PK, Murphy RF, Gillespie AJ, Poplack DG: Intrathecal 6–mercaptopurine: preclinical pharmacology, phase I/II trial and pharmacokinetic study. Cancer Res 51: 6079–6083, 1991

    Google Scholar 

  61. Zimm S, Ettinger L, Holcenberg JS, Kamen BA, Vietti TJ, Belasco J, Cogliano-Shuttan, Balis F, Lavi LE, Collins JM: Phase I and clinical pharmacological study of 6–mercaptopurine administered as a prolonged intravenous infusion. Cancer Res 45: 1869–1873, 1985

    Google Scholar 

  62. Fuchs HE, Archer GE, Colvin OM, Bigner SH, Schuster JM, Fuller GN, Muhlbaier LH, Schold SC Jr, Friedman HS, Bigner DD: Activity of intrathecal 4–hydroperoxycyclophosphamide in a nude rat model of human neoplastic meningitis. Cancer Res 50: 1954–1959, 1990

    Google Scholar 

  63. Friedman HS, Ochs J, Finlay J, Geyer R, Arndt C, Cohen B, Phillips P, Strauss LC, Hochberg F, Schold SC, Bigner DD, Colvin OM: Phase I trial of intrathecal 4–hydroperoxycyclophosphamide for neoplastic meningitis. Proc Am Assoc Cancer Res 34: 1598, 1993

    Google Scholar 

  64. Blaney SM, Cole DE, Godwin D, Sung C, Poplack DG, Balis FM: Intrathecal administration of topotecan in nonhuman primates. Cancer Chemother Pharmacol 36: 121–124, 1995

    Google Scholar 

  65. Galton GAG: Myleran in chronic myeloid leukemia: results of treatment. Lancet 1: 208–213, 1953

    Google Scholar 

  66. Friedman HS, Colvin OM, Skapek SX, Ludeman SM, Elion GB, Schold SC Jr, Jacobsen PF, Muhlbaier LH, Bigner DD: Experimental chemotherapy of human medulloblastoma cell lines and transplantable xenografts with bifunctional alkylating agents. Cancer Res 48: 4189–4195, 1988

    Google Scholar 

  67. Friedman HS, Schold SC Jr, Mahaley MS Jr: Phase II treatment of medulloblastoma and pineoblastoma with melphalan: clinical therapy based on experimental models of human medulloblastoma. J Clin Oncol 7: 904–919, 1989

    Google Scholar 

  68. Aaron RH, Elion GB, Colvin OM, Graham M, Keir S, Bigner DD, Friedman HS: Busulfan therapy of central nervous system xenografts in athymic mice. Cancer Chemother Pharmacol 35: 127–131, 1994

    Google Scholar 

  69. Coakham HB, Kemshead JT: Treatment of neoplastic meningitis by targeted radiation using 131I-radiolabelled monoclonal antibodies. J Neuro-Oncol 38: 225–232, 1998

    Google Scholar 

  70. Vrionis FD: Gene therapy of neoplastic meningosis. J Neuro-Oncol 38: 241–244. 1998

    Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA

    Ilkcan Cokgor

  2. Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA

    Allan H. Friedman

  3. Department of Pediatrics, Duke University Medical Center, Durham, NC, 27710, USA

    Henry S. Friedman

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  1. Ilkcan Cokgor
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  2. Allan H. Friedman
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  3. Henry S. Friedman
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Cokgor, I., Friedman, A.H. & Friedman, H.S. Current Options for the Treatment of Neoplastic Meningitis. J Neurooncol 60, 79–88 (2002). https://doi.org/10.1023/A:1020200317464

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