Journal of Korean Neurosurgical Society

The Korean Neurosurgical Society (대한신경외과학회)
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Recent Advancements of Treatment for Leptomeningeal Carcinomatosis

  • Gwak, Ho-Shin (Department of System Cancer Science, Graduate School of Cancer Science and Policy) ;
  • Lee, Sang Hyun (Department of Diagnostic Radiology, National Cancer Center) ;
  • Park, Weon Seo (Department of Pathology, National Cancer Center) ;
  • Shin, Sang Hoon (Department of Neuro-Oncology Clinic, National Cancer Center) ;
  • Yoo, Heon (Department of Neuro-Oncology Clinic, National Cancer Center) ;
  • Lee, Seung Hoon (Department of Neuro-Oncology Clinic, National Cancer Center)
  • Received : 2014.11.30
  • Accepted : 2015.02.16
  • Published : 2015.07.28
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Abstract

Treatment of Leptomeningeal carcinomatosis (LMC) from solid cancers has not advanced noticeably since the introduction of intra-cerebrospinal fluid (CSF) chemotherapy in the 1970's. The marginal survival benefit and difficulty of intrathecal chemotherapy injection has hindered its wide spread use. Even after the introduction of intraventricular chemotherapy with Ommaya reservoir, frequent development of CSF flow disturbance, manifested as increased intracranial pressure (ICP), made injected drug to be distributed unevenly and thus, the therapy became ineffective. Systemic chemotherapy for LMC has been limited as effective CSF concentration can hardly be achieved except high dose methotrexate (MTX) intravenous administration. However, the introduction of small molecular weight target inhibitors for primary cancer treatment has changed the old concept of 'blood-brain barrier' as the ultimate barrier to systemically administered drugs. Conventional oral administration achieves an effective concentration at the nanomolar level. Furthermore, many studies report that a combined treatment of target inhibitor and intra-CSF chemotherapy significantly prolongs patient survival. Ventriculolumbar perfusion (VLP) chemotherapy has sought to increase drug delivery to the subarachnoid CSF space even in patients with disturbed CSF flow. Recently authors performed phase 1 and 2 clinical trial of VLP chemotherapy with MTX, and 3/4th of patients with increased ICP got controlled ICP and the survival was prolonged. Further trials are required with newly available drugs for CSF chemotherapy. Additionally, new LMC biologic/pharmacodynamic markers for early diagnosis and monitoring of the treatment response are to be identified with the help of advanced molecular biology techniques.

Keywords

References

  1. Balis FM, Blaney SM, McCully CL, Bacher JD, Murphy RF, Poplack DG : Methotrexate distribution within the subarachnoid space after intraventricular and intravenous administration. Cancer Chemother Pharmacol 45 : 259-264, 2000 https://doi.org/10.1007/s002800050038
  2. Baraniskin A, Kuhnhenn J, Schlegel U, Schmiegel W, Hahn S, Schroers R : MicroRNAs in cerebrospinal fluid as biomarker for disease course monitoring in primary central nervous system lymphoma. J Neurooncol 109 : 239-244, 2012 https://doi.org/10.1007/s11060-012-0908-2
  3. Bernardi RJ, Bomgaars L, Fox E, Balis FM, Egorin MJ, Lagattuta TF, et al. : Phase I clinical trial of intrathecal gemcitabine in patients with neoplastic meningitis. Cancer Chemother Pharmacol 62 : 355-361, 2008 https://doi.org/10.1007/s00280-007-0601-x
  4. Blaney SM, Balis FM, Berg S, Arndt CA, Heideman R, Geyer JR, et al. : Intrathecal mafosfamide : a preclinical pharmacology and phase I trial. J Clin Oncol 23 : 1555-1563, 2005 https://doi.org/10.1200/JCO.2005.06.053
  5. Blaney SM, Boyett J, Friedman H, Gajjar A, Geyer R, Horowtiz M, et al. : Phase I clinical trial of mafosfamide in infants and children aged 3 years or younger with newly diagnosed embryonal tumors : a pediatric brain tumor consortium study (PBTC-001). J Clin Oncol 23 : 525-531, 2005 https://doi.org/10.1200/JCO.2005.06.544
  6. Blaney SM, Cole DE, Balis FM, Godwin K, Poplack DG : Plasma and cerebrospinal fluid pharmacokinetic study of topotecan in nonhuman primates. Cancer Res 53 : 725-727, 1993
  7. Blaney SM, Heideman R, Berg S, Adamson P, Gillespie A, Geyer JR, et al. : Phase I clinical trial of intrathecal topotecan in patients with neoplastic meningitis. J Clin Oncol 21 : 143-147, 2003 https://doi.org/10.1200/JCO.2003.04.053
  8. Blaney SM, Kocak M, Gajjar A, Chintagumpala M, Merchant T, Kieran M, et al. : Pilot study of systemic and intrathecal mafosfamide followed by conformal radiation for infants with intracranial central nervous system tumors : a pediatric brain tumor consortium study (PBTC-001). J Neurooncol 109 : 565-571, 2012 https://doi.org/10.1007/s11060-012-0929-x
  9. Blaney SM, Poplack DG : New cytotoxic drugs for intrathecal administration. J Neurooncol 38 : 219-223, 1998 https://doi.org/10.1023/A:1005944622003
  10. Blasberg RG, Patlak CS, Shapiro WR : Distribution of methotrexate in the cerebrospinal fluid and brain after intraventricular administration. Cancer Treat Rep 61 : 633-641, 1977
  11. Bokstein F, Lossos A, Lossos IS, Siegal T : Central nervous system relapse of systemic non-Hodgkin's lymphoma : results of treatment based on high-dose methotrexate combination chemotherapy. Leuk Lymphoma 43 : 587-593, 2002 https://doi.org/10.1080/10428190290012092
  12. 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 82 : 1756-1763, 1998 https://doi.org/10.1002/(SICI)1097-0142(19980501)82:9<1764::AID-CNCR24>3.0.CO;2-1
  13. 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 randomised study. Eur J Cancer 40 : 2726-2733, 2004 https://doi.org/10.1016/j.ejca.2004.08.012
  14. Bruna J, Gonzalez L, Miro J, Velasco R, Gil M, Tortosa A, et al. : Leptomeningeal carcinomatosis : prognostic implications of clinical and cerebrospinal fluid features. Cancer 115 : 381-389, 2009 https://doi.org/10.1002/cncr.24041
  15. Chamberlain MC : Leptomeningeal metastases : a review of evaluation and treatment. J Neurooncol 37 : 271-284, 1998 https://doi.org/10.1023/A:1005976926058
  16. Chamberlain MC : Radioisotope CSF flow studies in leptomeningeal metastases. J Neurooncol 38 : 135-140, 1998 https://doi.org/10.1023/A:1005982826121
  17. Chamberlain MC, Kormanik P : Carcinoma meningitis secondary to non-small cell lung cancer : combined modality therapy. Arch Neurol 55 : 506-512, 1998 https://doi.org/10.1001/archneur.55.4.506
  18. Chamberlain MC, Kormanik PA : Prognostic significance of 111indium-DTPA CSF flow studies in leptomeningeal metastases. Neurology 46 : 1674-1677, 1996 https://doi.org/10.1212/WNL.46.6.1674
  19. Chamberlain MC, Kormanik PA, Barba D : Complications associated with intraventricular chemotherapy in patients with leptomeningeal metastases. J Neurosurg 87 : 694-699, 1997 https://doi.org/10.3171/jns.1997.87.5.0694
  20. Clarke JL, Pao W, Wu N, Miller VA, Lassman AB : High dose weekly erlotinib achieves therapeutic concentrations in CSF and is effective in leptomeningeal metastases from epidermal growth factor receptor mutant lung cancer. J Neurooncol 99 : 283-286, 2010 https://doi.org/10.1007/s11060-010-0128-6
  21. de Azevedo CR, Cruz MR, Chinen LT, Peres SV, Peterlevitz MA, de Azevedo Pereira AE, et al. : Meningeal carcinomatosis in breast cancer : prognostic factors and outcome. J Neurooncol 104 : 565-572, 2011 https://doi.org/10.1007/s11060-010-0524-y
  22. Egorin MJ, Zuhowski EG, McCully CM, Blaney SM, Kerr JZ, Berg SL, et al. : Pharmacokinetics of intrathecal gemcitabine in nonhuman primates. Clin Cancer Res 8 : 2437-2442, 2002
  23. Fizazi K, Asselain B, Vincent-Salomon A, Jouve M, Dieras V, Palangie T, et al. : Meningeal carcinomatosis in patients with breast carcinoma. Clinical features, prognostic factors, and results of a high-dose intrathecal methotrexate regimen. Cancer 77 : 1315-1323, 1996 https://doi.org/10.1002/(SICI)1097-0142(19960401)77:7<1315::AID-CNCR14>3.0.CO;2-4
  24. Fleischhack G, Jaehde U, Bode U : Pharmacokinetics following intraventricular administration of chemotherapy in patients with neoplastic meningitis. Clin Pharmacokinet 44 : 1-31, 2005
  25. Freilich RJ, Krol G, DeAngelis LM : Neuroimaging and cerebrospinal fluid cytology in the diagnosis of leptomeningeal metastasis. Ann Neurol 38 : 51-57, 1995 https://doi.org/10.1002/ana.410380111
  26. Gauthier H, Guilhaume MN, Bidard FC, Pierga JY, Girre V, Cottu PH, et al. : Survival of breast cancer patients with meningeal carcinomatosis. Ann Oncol 21 : 2183-2187, 2010 https://doi.org/10.1093/annonc/mdq232
  27. 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 5 : 3394-3402, 1999
  28. Glass JP, Melamed M, Chernik NL, Posner JB : Malignant cells in cerebrospinal fluid (CSF) : the meaning of a positive CSF cytology. Neurology 29 : 1369-1375, 1979 https://doi.org/10.1212/WNL.29.10.1369
  29. Gleissner B, Chamberlain MC : Neoplastic meningitis. Lancet Neurol 5 : 443-452, 2006 https://doi.org/10.1016/S1474-4422(06)70443-4
  30. Grossman SA, Krabak MJ : Leptomeningeal carcinomatosis. Cancer Treat Rev 25 : 103-119, 1999 https://doi.org/10.1053/ctrv.1999.0119
  31. Grossman SA, Reinhard CS, Loats HL : The intracerebral penetration of intraventricularly administered methotrexate : a quantitative autoradiographic study. J Neurooncol 7 : 319-328, 1989 https://doi.org/10.1007/BF02147089
  32. Grossman SA, Trump DL, Chen DC, Thompson G, Camargo EE : Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using 111indium-DTPA ventriculography. Am J Med 73 : 641-647, 1982 https://doi.org/10.1016/0002-9343(82)90404-1
  33. Gururangan S, Petros WP, Poussaint TY, Hancock ML, Phillips PC, Friedman HS, et al. : Phase I trial of intrathecal spartaject busulfan in children with neoplastic meningitis : a Pediatric Brain Tumor Consortium Study (PBTC-004). Clin Cancer Res 12 : 1540-1546, 2006 https://doi.org/10.1158/1078-0432.CCR-05-2094
  34. Gwak HS, Joo J, Kim S, Yoo H, Shin SH, Han JY, et al. : Analysis of treatment outcomes of intraventricular chemotherapy in 105 patients for leptomeningeal carcinomatosis from non-small-cell lung cancer. J Thorac Oncol 8 : 599-605, 2013 https://doi.org/10.1097/JTO.0b013e318287c943
  35. Gwak HS, Joo J, Shin SH, Yoo H, Han JY, Kim HT, et al. : Ventriculolumbar perfusion chemotherapy with methotrexate for treating leptomeningeal carcinomatosis : a Phase II Study. Oncologist 19 : 1044-1045, 2014 https://doi.org/10.1634/theoncologist.2014-0199
  36. Gwak HS, Lim HS, Shin SH, Yoo H, Han JY, Kim HT, et al. : Ventriculolumbar perfusion chemotherapy for the treatment of leptomeningeal carcinomatosis : a phase I study with pharmacokinetic data. Am J Clin Oncol 36 : 491-499, 2013 https://doi.org/10.1097/COC.0b013e3182549643
  37. Herrlinger U, Forschler H, Kuker W, Meyermann R, Bamberg M, Dichgans J, et al. : Leptomeningeal metastasis : survival and prognostic factors in 155 patients. J Neurol Sci 223 : 167-178, 2004 https://doi.org/10.1016/j.jns.2004.05.008
  38. 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 https://doi.org/10.1200/JCO.1987.5.10.1655
  39. Hofer S, Mengele K, Stemmler HJ, Schmitt M, Pestalozzi B : Intrathecal trastuzumab : dose matters. Acta Oncol 51 : 955-956, 2012 https://doi.org/10.3109/0284186X.2012.673736
  40. Katayama T, Shimizu J, Suda K, Onozato R, Fukui T, Ito S, et al. : Efficacy of erlotinib for brain and leptomeningeal metastases in patients with lung adenocarcinoma who showed initial good response to gefitinib. J Thorac Oncol 4 : 1415-1419, 2009 https://doi.org/10.1097/JTO.0b013e3181b62572
  41. Kim DY, Lee KW, Yun T, Park SR, Jung JY, Kim DW, et al. : Comparison of intrathecal chemotherapy for leptomeningeal carcinomatosis of a solid tumor : methotrexate alone versus methotrexate in combination with cytosine arabinoside and hydrocortisone. Jpn J Clin Oncol 33 : 608-612, 2003 https://doi.org/10.1093/jjco/hyg118
  42. Laufman LR, Forsthoefel KF : Use of intrathecal trastuzumab in a patient with carcinomatous meningitis. Clin Breast Cancer 2 : 235, 2001 https://doi.org/10.1016/S1526-8209(11)70419-0
  43. Levin VA, Byrd D, Campbell J, Giannini DD, Borcich JK, Davis RL : Central nervous system toxicity and cerebrospinal fluid pharmacokinetics of intraventricular 3-[(4-amino-2-methyl-5-pyrimidinyl)ethyl]-1-(2-chloroethyl)-1-nitro soureas and other nitrosoureas in beagles. Cancer Res 45 : 3803-3809, 1985
  44. Levin VA, Chamberlain M, Silver P, Rodriguez L, Prados M : Phase I/II study of intraventricular and intrathecal ACNU for leptomeningeal neoplasia. Cancer Chemother Pharmacol 23 : 301-307, 1989 https://doi.org/10.1007/BF00292408
  45. Liu S, Sun J, Lan Q : Glioblastoma microvesicles promote endothelial cell proliferation through Akt/beta-catenin pathway. Int J Clin Exp Pathol 7 : 4857-4866, 2014
  46. Masuda T, Hattori N, Hamada A, Iwamoto H, Ohshimo S, Kanehara M, et al. : Erlotinib efficacy and cerebrospinal fluid concentration in patients with lung adenocarcinoma developing leptomeningeal metastases during gefitinib therapy. Cancer Chemother Pharmacol 67 : 1465-1469, 2011 https://doi.org/10.1007/s00280-011-1555-6
  47. Mittl RL Jr, Yousem DM : Frequency of unexplained meningeal enhancement in the brain after lumbar puncture. AJNR Am J Neuroradiol 15 : 633-638, 1994
  48. Morris PG, Reiner AS, Szenberg OR, Clarke JL, Panageas KS, Perez HR, et al. : Leptomeningeal metastasis from non-small cell lung cancer : survival and the impact of whole brain radiotherapy. J Thorac Oncol 7 : 382-385, 2012 https://doi.org/10.1097/JTO.0b013e3182398e4f
  49. Nakagawa H, Fujita T, Kubo S, Izumoto S, Nakajima Y, Tsuruzono K, et al. : Ventriculolumbar perfusion chemotherapy with methotrexate and cytosine arabinoside for meningeal carcinomatosis : a pilot study in 13 patients. Surg Neurol 45 : 256-264, 1996 https://doi.org/10.1016/0090-3019(95)00403-3
  50. 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 33 : 1565-1572, 1983 https://doi.org/10.1212/WNL.33.12.1565
  51. Park JH, Kim YJ, Lee JO, Lee KW, Kim JH, Bang SM, et al. : Clinical outcomes of leptomeningeal metastasis in patients with non-small cell lung cancer in the modern chemotherapy era. Lung Cancer 76 : 387-392, 2012 https://doi.org/10.1016/j.lungcan.2011.11.022
  52. Rubin RC, Ommaya AK, Henderson ES, Bering EA, Rall DP : Cerebrospinal fluid perfusion for central nervous system neoplasms. Neurology 16 : 680-692, 1966 https://doi.org/10.1212/WNL.16.7.680
  53. Sato Y, Ohta Y, Kaji M, Oizumi K, Kaji M : Carbohydrate antigen 19-9 in cerebrospinal fluid and within malignant cells in a case of leptomeningeal carcinomatosis. J Neurol Neurosurg Psychiatry 65 : 402-403, 1998 https://doi.org/10.1136/jnnp.65.3.402
  54. Schabet M, Kloeter I, Adam T, Heidemann E, Wietholter H : Diagnosis and treatment of meningeal carcinomatosis in ten patients with breast cancer. Eur Neurol 25 : 403-411, 1986 https://doi.org/10.1159/000116043
  55. Shapiro WR, Young DF, Mehta BM : Methotrexate : distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med 293 : 161-166, 1975 https://doi.org/10.1056/NEJM197507242930402
  56. Siegal T, Lossos A, Pfeffer MR : Leptomeningeal metastases : analysis of 31 patients with sustained off-therapy response following combined-modality therapy. Neurology 44 : 1463-1469, 1994 https://doi.org/10.1212/WNL.44.8.1463
  57. Straathof CS, de Bruin HG, Dippel DW, Vecht CJ : The diagnostic accuracy of magnetic resonance imaging and cerebrospinal fluid cytology in leptomeningeal metastasis. J Neurol 246 : 810-814, 1999 https://doi.org/10.1007/s004150050459
  58. Swinkels DW, de Kok JB, Hanselaar A, Lamers K, Boerman RH : Early detection of leptomeningeal metastasis by PCR examination of tumor-derived K-ras DNA in cerebrospinal fluid. Clin Chem 46 : 132-133, 2000
  59. Taillibert S, Laigle-Donadey F, Chodkiewicz C, Sanson M, Hoang-Xuan K, Delattre JY : Leptomeningeal metastases from solid malignancy : a review. J Neurooncol 75 : 85-99, 2005 https://doi.org/10.1007/s11060-004-8101-x
  60. Teplyuk NM, Mollenhauer B, Gabriely G, Giese A, Kim E, Smolsky M, et al. : MicroRNAs in cerebrospinal fluid identify glioblastoma and metastatic brain cancers and reflect disease activity. Neuro Oncol 14 : 689-700, 2012 https://doi.org/10.1093/neuonc/nos074
  61. Tetef ML, Margolin KA, Doroshow JH, Akman S, Leong LA, Morgan RJ Jr, et al. : Pharmacokinetics and toxicity of high-dose intravenous methotrexate in the treatment of leptomeningeal carcinomatosis. Cancer Chemother Pharmacol 46 : 19-26, 2000 https://doi.org/10.1007/s002800000118
  62. Tran HC, Gardner S, Weiner HL, Liebes LF, Finlay JL : Pilot study assessing a seven-day continuous intrathecal topotecan infusion for recurrent or progressive leptomeningeal metastatic cancer. J Oncol Pharm Pract 20 : 229-232, 2014 https://doi.org/10.1177/1078155213494940
  63. Twijnstra A, van Zanten AP, Hart AA, Ongerboer de Visser BW : Serial lumbar and ventricle cerebrospinal fluid lactate dehydrogenase activities in patients with leptomeningeal metastases from solid and haematological tumours. J Neurol Neurosurg Psychiatry 50 : 313-320, 1987 https://doi.org/10.1136/jnnp.50.3.313
  64. Twijnstra A, van Zanten AP, Nooyen WJ, Ongerboer de Visser BW : Sensitivity and specificity of single and combined tumour markers in the diagnosis of leptomeningeal metastasis from breast cancer. J Neurol Neurosurg Psychiatry 49 : 1246-1250, 1986 https://doi.org/10.1136/jnnp.49.11.1246
  65. Waki F, Ando M, Takashima A, Yonemori K, Nokihara H, Miyake M, et al. : Prognostic factors and clinical outcomes in patients with leptomeningeal metastasis from solid tumors. J Neurooncol 93 : 205-212, 2009 https://doi.org/10.1007/s11060-008-9758-3
  66. Wasserstrom WR, Glass JP, Posner JB : Diagnosis and treatment of leptomeningeal metastases from solid tumors : experience with 90 patients. Cancer 49 : 759-772, 1982 https://doi.org/10.1002/1097-0142(19820215)49:4<759::AID-CNCR2820490427>3.0.CO;2-7
  67. Yi HG, Kim HJ, Kim YJ, Han SW, Oh DY, Lee SH, et al. : Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective for leptomeningeal metastasis from non-small cell lung cancer patients with sensitive EGFR mutation or other predictive factors of good response for EGFR TKI. Lung Cancer 65 : 80-84, 2009 https://doi.org/10.1016/j.lungcan.2008.10.016
  68. Yousem DM, Patrone PM, Grossman RI : Leptomeningeal metastases : MR evaluation. J Comput Assist Tomogr 14 : 255-261, 1990 https://doi.org/10.1097/00004728-199003000-00018
  69. Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, et al. : Intrathecal administration of trastuzumab for the treatment of meningeal carcinomatosis in HER2-positive metastatic breast cancer : a systematic review and pooled analysis. Breast Cancer Res Treat 139 : 13-22, 2013 https://doi.org/10.1007/s10549-013-2525-y

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