Seminars in Oncology
Volume 36 , Pages S46-S54 , August 2009

Treatment Modalities for Leptomeningeal Metastases

  • William R. Shapiro

      Affiliations

    • Division of Neurology, Director Neuro-Oncology Program, Barrow Neurological Institute, Phoenix, AZ
    • Corresponding Author InformationAddress correspondence to William R. Shapiro, MD, Division of Neurology, Barrow Neurological Institute, 350 West Thomas Rd, Phoenix, AZ 85013
    • ,
  • Conrad E. Johanson

      Affiliations

    • Department of Clinical Neurosciences, Warren Alpert Medical School at Brown University, Providence, RI
    • ,
  • Willem Boogerd

      Affiliations

    • Department of Neuro-oncology, Netherlands Cancer Institute, Amsterdam, Netherlands

References 

  1. Chamberlain MC. Neoplastic meningitis. Neurologist. 2006;12:179–187
  2. Jaeckle KA. Neoplastic meningitis from systemic malignancies; diagnosis, prognosis and treatment. Semin Oncol. 2006;33:312–323
  3. Kesari S, Batchelor TT. Leptomeningeal metastases. Neurol Clin. 2003;21:25–66
  4. Gleissner B, Chamberlain MC. Neoplastic meningitis. Lancet Neurol. 2006;5:443–452
  5. Johanson CE, Duncan JA, Stopa EG, Baird A. Enhanced prospects for drug delivery and brain targeting by the choroid plexus-CSF route. Pharm Res. 2005;22:1011–1037
  6. Habgood MD, Begley DJ, Abbott NJ. Determinants of passive drug entry into the central nervous system. Cell Mol Neurobiol. 2000;20:231–253
  7. Ghersi-Egea JF, Leininger-Muller B, Cecchelli R, Fenstermacher JD. Blood-brain interfaces: relevance to cerebral drug metabolism. Toxicol Lett. 1995;82–83645-53
  8. Grant R, Naylor B, Greenberg HS, Junck L. Clinical outcome in aggressively treated meningeal carcinomatosis. Arch Neurol. 1994;51:457–461
  9. Glantz MJ, Cole BF, Recht L, Akerley W, Mills P, Saris S, et al. High-dose intravenous methotrexate for patients with nonleukemic leptomeningeal cancer: is intrathecal chemotherapy necessary?. J Clin Oncol. 1998;16:1561–1567
  10. Shapiro WR, Young DF, Mehta BM. Methotrexate distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med. 1975;293:161–166
  11. Balis RM, Blaney SM, McCully CL, Bacher JD, Jurphy RF, Poplack DG. Methotrexate distribution within the subarachnoid space after intraventricular and intravenous administration. Cancer Chemother Pharmacol. 2000;45:259–264
  12. Hryniuk WM, Bertino JR. Treatment of leukemia with large doses of methotrexate and folinic acid: clinical-biomedical correlates. J Clin Invest. 1969;48:2140–2155
  13. Chabner BA, Young R. Threshold methotrexate concentration for in vivo inhibition of DNA synthesis in normal and tumorous target tissues. J Clin Invest. 1973;52:1804–1811
  14. Green MR, Chowdhary S, Lombardi KM, Chalmers LM, Chamberlain M. Clinical utility and pharmacology of high-dose methotrexate in the treatment of primary CNS lymphoma. Expert Rev Neurother. 2006;6:635–652
  15. Strother DR, Glynn-Barnhart A, Kovnar E. Variability in the disposition of intraventricular methotrexate: A proposal for rational dosing. J Clin Oncol. 1989;7:1741–1747
  16. Bleyer WA, Drake JC, Chabner BA. Neurotoxicity and elevated cerebrospinal-fluid methotrexate concentration in meningeal leukemia. N Engl J Med. 1973;289:770–773
  17. Lopez JA, Nassif E, Vannicola P, Krikorian JG, Agarwal RP. Central nervous system pharmacokinetics of high-dose cytosine arabinoside. J Neurooncol. 1985;3:119–124
  18. Slevin ML, Piall EM, Aherne GW, Harvey VJ, Johnston A, Lister TA. Effect of dose and schedule on pharmacokinetics of high-dose cytosine arabinoside in plasma and cerebrospinal fluid. J Clin Oncol. 1983;1:546–551
  19. DeAngelis LM, Kreis W, Chan K, Dantis E, Akerman S. Pharmacokinetics of ara-C and ara-U in plasma and CSF after high-dose administration of cytosine arabinoside. Cancer Chemother Pharmacol. 1992;29:173–177
  20. Sutoh H, Yamauchi T, Gotoh N, Sugiyama M, Ueda T. Pharmacological study of modified intermediate-dose cytarabine therapy in patients with acute myeloid leukemia. Anticancer Res. 2003;23:5037–5042
  21. Muldoon LL, Soussain C, Jahnke K, Johanson C, Siegal T, Smith QR, et al. Chemotherapy delivery issues in central nervous system malignancy: a reality check. J Clin Oncol. 2007;25:2295–2305
  22. Kim L, Glantz MJ. Neoplastic meningitis. Curr Treat Options Oncol. 2001;2:517–527
  23. Grossman SA, Reinhard CS, Loats HL. The intracerebral penetration of intraventricularly administered methotrexate: a quantitative autoradiographic study. J Neurooncol. 1989;7:319–328
  24. Burch PA, Grossman SA, Reinhard CS. Spinal cord penetration of intrathecally administered cytarabine and methotrexate: a quantitative autoradiographic study. J Natl Cancer Inst. 1988;80:1211–1216
  25. Blasberg RG, Patlak C, Fenstermacher JD. Intrathecal chemotherapy: brain tissue profiles after ventriculocisternal perfusion. J Pharmacol Exp Ther. 1975;195:73–83
  26. Blasberg RG, Patlak CS, Shapiro WR. Distribution of methotrexate in the cerebrospinal fluid and brain after intraventricular administration. Cancer Treat Rep. 1977;61:633–641
  27. Blasberg RG. Methotrexate, cytosine arabinoside, and BCNU concentration in brain after ventriculocisternal perfusion. Cancer Treat Rep. 1977;61:625–631
  28. Bleyer WA, Poplack DG. Intraventricular versus intralumbar methotrexate for central-nervous-system leukemia: Prolonged remission with the Ommaya reservoir. Med Pediatr Oncol. 1979;6:207–213
  29. Glantz MJ, Jaeckle KA, Chamberlain MC, Phuphanich S, Recht L, Swinnen LJ, et al. A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors. Clin Cancer Res. 1999;5:3394–3402
  30. Kim S, Khatibi S, Howell SB, McCully C, Balis FM, Poplack DG. Prolongation of drug exposure in cerebrospinal fluid by encapsulation into DepoFoam. Cancer Res. 1993;53:1596–1598
  31. Rueda Dominguez A, Olmos Hidalgo D, Viciana Garrido R, Torres Sanchez E. Liposomal cytarabine (DepoCyte) for the treatment of neoplastic meningitis. Clin Transl Oncol. 2005;7:232–238
  32. Chamberlain MC, Kormanik P, Howell SB, Kim S. Pharmacokinetics of intralumbar DTC-101 for the treatment of leptomeningeal metastases. Arch Neurol. 1995;52:912–917
  33. Cytarabine prescribing information. Bedford, OH: Bedford Laboratories; 2000;
  34. Methotrexate prescribing information. Floral, KY: Xanodyne Pharmacal Inc; 2003;
  35. Glantz MJ, Hall WA, Cole BF, Chozick BS, Shannon CM, Wahlberg L, et al. Diagnosis, management, and survival of patients with leptomeningeal cancer based on cerebrospinal fluid-flow status. Cancer. 1995;75:2919–2931
  36. Chamberlain MC, Kormanik PA, Barba D. Complications associated with intraventricular chemotherapy in patients with leptomeningeal metastases. J Neurosurg. 1997;87:694–699
  37. Siegal T, Lossos A, Pfeffer MR. Leptomeningeal metastases: analysis of 31 patients with sustained off-therapy response following combined-modality therapy. Neurology. 1994;44:1463–1469
  38. Boogerd W, van der Sande JJ, Moffie D. Acute fever and delayed leukoencephalopathy following low dose intraventricular methotrexate. J Neurol Neurosurg Psychiatry. 1988;51:1277–1283
  39. Grossman SA, Krabak MJ. Leptomeningeal carcinomatosis. Cancer Treat Rev. 1999;25:103–119
  40. Grossman SA, Trump DL, Chen DC, Thompson G, Camargo EE. Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis (An evaluation using 111 indium-DTPA ventriculography). Am J Med. 1982;73:641–647
  41. Chamberlain MC, Corey-Bloom J. Leptomeningeal metastases: 111 indium-DTPA CSF flow studies. Neurology. 1991;41:1765–1769
  42. Chamberlain MC, Kormanik PA. Prognostic significance of 111 indium-DTPA CSF flow studies in leptomeningeal metastases. Neurology. 1996;46:1674–1677
  43. Mason WP, Yeh SD, DeAngelis LM. 111 Indium-diethylenetriamine pentaacetic acid cerebrospinal fluid flow studies predict distribution of intrathecally administered chemotherapy and outcome in patients with leptomeningeal metastases. Neurology. 1998;50:438–444
  44. Chamberlain MC, Nolan C, Abrey LE. Leukemic and lymphomatous meningitis: incidence, prognosis and treatment. J Neurooncol. 2005;75:71–83
  45. Chamberlain MC. Chemotherapy for brain metastases due to lung cancer and melanoma. Cancer Treat Res. 2007;136:199–213
  46. Price SA, Polk HC. Prophylactic and therapeutic use of antibiotics in pelvic surgery. J Surg Oncol. 1999;71:261–268
  47. Page CP, Bohnen JM, Fletcher JR, McManus AT, Solomkin JS, Wittmann DH. Antimicrobial prophylaxis for surgical wounds (Guidelines for clinical care). Arch Surg. 1993;128:79–88
  48. Shapiro WR, Posner JB, Ushio Y, Chemik NL, Young DF. Treatment of meningeal neoplasms. Cancer Treat Rep. 1977;61:733–743
  49. Wasserstrom WR, Glass JP, Posner JB. Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients. Cancer. 1982;49:759–772
  50. Yap HY, Yap BS, Rasmussen S, Levens ME, Hortobagyi GN, Blumenschein GR. Treatment for meningeal carcinomatosis in breast cancer. Cancer. 1982;50:219–222
  51. Ongerboer de Visser BW, Somers R, Nooyen WH, van Heerde P, Hart AA, McVie JG. Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma. Neurology. 1983;33:1565–1572
  52. Clamon G, Doebbeling B. Meningeal carcinomatosis from breast cancer: spinal cord vs. brain involvement. Breast Cancer Res Treat. 1987;9:213–217
  53. Jayson GC, Howell A, Harris M, Morgenstern G, Chang J, Ryder WD. Carcinomatous meningitis in patients with breast cancer (An aggressive disease variant). Cancer. 1994;74:3135–3141
  54. Boogerd W, Hart AA, van der Sande JJ, Engelsman E. Meningeal carcinomatosis in breast cancer (Prognostic factors and influence of treatment). Cancer. 1991;67:1685–1695
  55. Bokstein F, Lossos A, Siegal T. Leptomeningeal metastases from solid tumors: a comparison of two prospective series treated with and without intra-cerebrospinal fluid chemotherapy. Cancer. 1998;82:1756–1763
  56. Hitchins RN, Bell DR, Woods RL, Levi JA. A prospective randomized trial of single-agent versus combination chemotherapy in meningeal carcinomatosis. J Clin Oncol. 1987;5:1655–1662
  57. 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 (Eastern Cooperative Oncology Group). J Clin Oncol. 1993;11:561–569
  58. Boogerd W, van den Bent MJ, Koehler PJ, Heimans JJ, van der Sande JJ, Aaronson NK, et al. The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: a randomized study. Eur J Cancer. 2004;40:2726–2733
  59. Clatot F, Ouvrier M, Guillemet C, Veyret C, Blot E. Correlation of normalization of cerebrospinal fluid cytology (CSFC) with survival in breast cancer-related malignant meningitis (BMM) [abstract 1108]. Poster presented at the 44th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 30-June 3, 2008.
  60. Kim S, Chatelut E, Kim JC, Howell SB, Cates C, Kormanik PA, et al. Extended CSF cytarabine exposure following intrathecal administration of DTC 101. J Clin Oncol. 1993;11:2186–2193
  61. Phuphanich S, Maria B, Braeckman R, Chamberlain M. A pharmacokinetic study of intra-CSF administered encapsulated cytarabine (DepoCyt) for the treatment of neoplastic meningitis in patients with leukemia, lymphoma, or solid tumors as part of a phase III study. J Neurooncol. 2007;81:201–208
  62. Johanson CE. Choroid plexus-cerebrospinal fluid circulatory dynamics: impact on brain growth, metabolism, and repair. In:  Conn PM editors. Neuroscience in medicine. Totowa, NJ: Humana Press; 2008;p. 173–200
  63. Johanson CE, Duncan JA, Klinge PM, Brinker T, Stopa EG, Silverberg GD. Multiplicity of cerebrospinal fluid functions: new challenges in health and disease. Cerebrospinal Fluid Res. 2008;5:10
  64. Johanson CE. Arachnoid membrane, subarachnoid CSF and pia-glia. In:  Pardridge W editors. An introduction to the blood-brain barrier: methodology and biology. Cambridge: Cambridge University Press; 1998;p. 259–269
  65. Mangurian LP, Walsh RJ, Posner BI. Prolactin enhancement of its own uptake at the choroid plexus. Endocrinology. 1992;131:698–702
  66. Angelow S, Haselbach M, Galla HJ. Functional characterization of the active ascorbic acid transport into cerebrospinal fluid using primary cultured choroid plexus cells. Brain Res. 2003;988:105–113
  67. Petito CK. Human immunodeficiency virus type 1 compartmentalization in the central nervous system. J Neurovirol. 2004;10(Suppl 1):21–24
  68. Chen H, Wood C, Petito CK. Comparisons of HIV-1 viral sequences in brain, choroid plexus and spleen: potential role of choroid plexus in the pathogenesis of HIV encephalitis. J Neurovirol. 2000;6:498–506
  69. Levine S. Choroid plexus: target for systemic disease and pathway to the brain. Lab Invest. 1987;56:231–233
  70. Kivisäkk P, Mahad DJ, Callahan MK, Trebst C, Tucky B, Wei T, et al. Human cerebrospinal fluid central memory CD4+ T cells: evidence for trafficking through choroid plexus and meninges via P-selectin. Proc Natl Acad Sci U S A. 2003;100:8389–8394
  71. Chodobski A, Chung I, Koüniewska E, Ivanenko T, Chang W, Harrington JF, et al. Early neutrophilic expression of vascular endothelial growth factor after traumatic brain injury. Neuroscience. 2003;122:853–867
  72. Oldstone MB, Southern PJ. Trafficking of activated cytotoxic T lymphocytes into the central nervous system: use of a transgenic model. Neuroimmunology. 1993;46:25–31
  73. Lampson LA. New animal models to probe brain tumor biology, therapy, and immunotherapy: advantages and remaining concerns. J Neurooncol. 2001;53:275–287

 STATEMENT OF CONFLICT OF INTEREST: The authors have nothing to disclose.

PII: S0093-7754(09)00096-7

doi: 10.1053/j.seminoncol.2009.05.006

Seminars in Oncology
Volume 36 , Pages S46-S54 , August 2009

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