Abstract
Introduction
Intrathecal chemotherapy is being explored in medulloblastoma in pre-school children as part of brain-sparing strategies and as an alternative to unacceptably neurotoxic cranio-spinal radiotherapy. The range of drugs suitable for this route of administration is restricted by the lack of research evidence of pharmacological suitability and efficacy of other drugs in medulloblastoma.
Methods
Ideal clinical, biological, physicochemical and pharmaceutical properties for intrathecal administration were defined through literature review of pharmaceutical texts, Medline, Embase and consulting the manufacturers. A total of 126 chemotherapy agents were assessed against these criteria by searching the academic domain of pharmaceutical texts, computer databases and consultation with manufacturers.
Results
Of the 126 candidate drugs, 99 were rejected because of documentation of their irritant nature, neurotoxicity and requirement for hepatic activation in standard pharmaceutical texts. Fifty were rejected for a single identifiable reason including, neurotoxicity (n = 24), irritant (n = 15), needs enzyme activation (n = 5), clinical evidence of intrathecal neurotoxicity (n = 4) and no evidence of tumour-specific efficacy (n = 2). Where two reasons were cited the justifications were: neurotoxic and irritant (n = 3) and needs activation and systemic administration results in equivalent concentration (n = 1). Twenty-seven drugs remained of which 12 were selected as eligible for further clinical investigation, and 15 were selected for further pre-clinical investigation.
Conclusions
The pre-determined criteria were not applicable, in their entirety, in the majority of drugs, due to lack of information in the academic domain, emphasising the importance of a more open approach for sharing basic drug information. The prioritised list of 12 candidate drugs for clinical trial and 15 for pre-clinical investigation justify that a concerted research effort in this area of practice is made.
Similar content being viewed by others
References
Interactive analysis LogP and LogW Predictors. http://www.logp.com
Aaron R, Elion G, Colvin O, Graham M, Keir S, Bigner D, Friedman H (1994) Busulfan therapy of central nervous system xenografts in athymic mice. Cancer Chemother Pharmacol 35:127–131
Allinson R, Stach P (1978) Intrathecal drug therapy. Drug Intell Clin Pharmacy 12:347–359
Archer G, Sampson J, McLendon R, Friedman A, Colvin O, Rose M, Sands H, McCullough W, Fuchs H, Bigner D, Friedman H (1999) Intrathecal busulfan treatment of human neoplastic meningitis in athymic nude rats. J Neurooncol 44:233–241
Arita N, Ushio Y, Hayakawa T, Nagatani M, Huang T-Y, Izumoto S, Mogami H (1988) Intrathecal ACNU—a new therapeutic approach against malignant leptomeningeal tumors. J Neurooncol 6:221–226
Arndt C, Colvin O, Balis F, Lester C, Johnson G, Poplack D (1987) Intrathecal administration of 4-hydroperoxycyclophosphamide in rhesus monkeys. Cancer Res 47:5932–5934
Ashley D, Merchant T, Zhou T, Coleman L, Pollack I, Duffner P, Burger P, Miller D, Buxton A, Douglas S (2008) Systemic chemotherapy, second-look surgery and conformal radiation therapy limited to the posterior fossa and primary site for children >8 months and <3 years with non-metastatic medulloblastoma: a Children’s Oncology Group phase III study. Neurooncology 10:436–437
Association of the British Pharmaceutical Industry (1999) ABPI Compendium of data sheets and summaries of product characteristics 1999–2000. Datapharm Publications, London
Baker S, Heideman RL, Crom WR, Kuttesch J, Gajjar A, Stewart C (1996) Cerebrospinal fluid pharmacokinetics and penetration of continuous infusion Topotecan in children with central nervous system tumours. Cancer Chemother Pharmacol 37:195–202
Bates S, Raphaelson M, Price R, McKeever P, Cohen S, Poplack D (1985) Ascending myelopathy after chemotherapy for central nervous system acute lymphoblastic leukemia: correlation with cerebrospinal fluid myelin basic protein. Med Pediatr Oncol 13:4–8
Bayer (1999) Information from medical information department. Newbury, Berkshire
Bender J, Grillo-Lopez A, Posada Jnr J (1983) Diaziquone (AZQ). Investig New Drugs 1:71–84
Berg S, Balis F, Zimm S, Murphy R, Holcenberg J, Sato J, Reaman G, Steinherz P, Gillespie A, Doherty K, Poplack D (1992) Phase I/II trial and pharmacokinetics of intrathecal diaziquone in refractory meningeal malignancies. J Clin Oncol 10:143–148
Bernardi R, Bomgaars L, Fox E, Balism F, Egorin M, Lagattuta T, Aikin A, Whitcome P, Renbarger J, Lieberman F, Berg S, Blaney S (2008) Phase I clinical trial of intrathecal gemcitabine in patients with neoplastic meningitis. Cancer Chemother Pharmacol 62:355–361
Bhojwani D, Pui C-H (2008) Intrathecal liposomal cytarabine: more friend than foe? Leuk Lymphoma 49:1427–1430
Blaney S, Boyett J, Friedman H, Gajjar A, Geyer R, Horowitz M, Hunt D, Kieran M, Kun L, Packer R, Phillips P, Pollack M, Prados M, Heideman R (2005) 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
Blaney S, Cole D, Godwin K, Sung C, Poplack D, Balis F (1995) Intrathecal administration of topotecan in nonhuman primates. Cancer Chemother Pharmacol 36:121–124
Blaney S, Heideman R, Berg S, Adamson P, Gillespie A, Geyer J, Packer R, Matthay K, Jaeckle K, Cole D, Kuttesch N, Poplack D, Ballis F (2003) Phase I clinical trial of intrathecal topotecan in patients with neoplastic meningitis. J Clin Oncol 21:143–147
Blaney S, Poplack D (1996) Pharmacologic strategies for the treatment of meningeal malignancy. Investig New Drugs 14:69–85
Blaney S, Poplack D (1998) New cytotoxic drugs for intrathecal administration. J Neurooncol 38:219–223
Bleyer W (1999) Intrathecal depot cytarabine therapy: a welcome addition to a limited armametarium. Clin Cancer Res 5:3349–3351
Bleyer W, Coccia P, Sather H et al (1983) Reduction in central nervous system leukemia with a pharmacokinetically derived intrathecal methotrexate dosage regimen. J Clin Oncol 1:317–325
Bleyer W, Drake J, Chabner B (1973) Neurotoxicity and elevated cerebrospinal fluid methotrexate concentration in meningeal leukemia. N Engl J Med 289:770–773
Boiardi A, Eoli M, Pozzi A, Salmaggi A, Broggi G, Silvani A (1999) Locally delivered chemotherapy and repeated surgery can improve survival in glioblastoma patients. Ital J Neurol Sci 20:43–48
Boland I, Vassal G, Morizet J, Terrier-Lacombe M-J, Valteau-Couanet D, Kalifa C, Hartmann O, Gouyette A (1999) Busulphan is active against neuroblastoma and medulloblastoma xenografts in athymic mice at clinically achievable plasma drug concentrations. Br J Cancer 79:787–792
Bomgaars L, Geyer J, Franklin J, Dahl G, Park J, Winick N, Klenke R, Berg S, Blaney S (2004) Phase I trial of intrathecal liposomal cytarabine in children with neoplastic meningitis. J Clin Oncol 19:3916–3921
Brandes A, Pasetto L, Monfardini S (2000) New drugs in recurrent high grade gliomas. Anti-Cancer Res 20:1913–1920
Brem H, Piantadosi S, Burger P, Walker M, Selker R, Vick N, Black K, Sisti M, Brem S, Mohr G, Muller P, Morawetz R, Schold S (1995) Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. Lancet 345:1008–1012
British Medical Association & Royal Pharmaceutical Society of Great Britain (2000) British National Formulary. BMA & RPS (GB), London
Castleberry R, Ragab A, Steuber C, Kamen B, Toledano S, Starling K, Norris D, Burger P, Krischer J (1990) Aziridinylbenzoquinone (AZQ) in the treatment of recurrent pediatric brain and other malignant solid tumors. Investig New Drugs 8:401–406
Chamberlain M, Khatibi S, Kim J, Howell S, Chatelut E, Kim S (1993) Treatment of leptomeningeal metastasis with intraventricular administration of depot cytarabine (DTC101). Arch Neurol 50:261–264
Chamberlain M, Kormanik P, Howell S, Kim S (1995) Pharmacokinetics of intralumbar DTC-101 for the treatment of leptomeningeal metastases. Arch Neurol 52:912–917
Champagne M, Silver H (1992) Intrathecal dacarbazine treatment of leptomeningeal malignant melanoma. J Natl Cancer Inst 84:1203–1204
Chen Y-M, Chen M-C, Tsai C-M, Perng R-P (2003) Intrathecal gemcitabine chemotherapy for non-small cell lung cancer patients with meningeal carcinomatosis—a case report. Lung Cancer 40:99–101
Crawford S, Rustin G, Bagshawe K (1986) Acute neurological toxicity of intrathecal cytosine arabinoside. Cancer Chemother Pharmacol 16:306–307
Damon L, Plunkett W, Linker C (1991) Plasma and cerebrospinal fluid pharmacokinetics of 1-β-d-arabinofuranosylcytosine and 1-β-d-arabinofuranosyluracil following the repeated intravenous administration of high- and intermediate-dose β-d-arabinofuranosylcytosine. Cancer Res 51:4141–4145
Department of Health (2008) Updated national guidance on the safe administration of intrathecal chemotherapy. In: Health Do (ed)
Dodion P, Sanders C, Georges P, Kenis Y (1988) In vitro chemosensitivity of brain tumors to cisplatin and its analogues, iproplatin and carboplatin. Cancer Chemother Pharmacol 22:80–82
Dollery C (ed) (1999) Therapeutic drugs. Churchill Livingstone, Edinburgh
Doz F, Pinkerton R (1994) What is the place of carboplatin in paediatric oncology? Eur J Cancer 30A:194–201
Drayton C (ed) (1990) Comprehensive medicinal chemistry. Pergamon Press, Oxford
Eagan R, Dinapoli R, Cascino T, Scheithauer B, O’Neill B, O’Fallon R (1987) Comprehensive phase II evaluation of Aziridinylbenzoquinone (AZQ, Diaziquone) in recurrent human primary brain tumors. J Neurooncol 5:309–314
Edwards M, Levin V, Seager M, Wilson C (1981) Intrathecal chemotherapy for leptomeningeal dissemination of medulloblastoma. Child’s Brain 8:444–451
Egorin M, Zuhowski E, McCully C, Blaney S, Kerr J, Berg S, Ballis F (2002) Pharmacokinetics of intrathecal gemcitabine in non-human primates. Clin Cancer Res 8:2437–2442
Englehard H (2000) The role of interstitial BCNU chemotherapy in the treatment of malignant glioma. Surg Neurol 53:458–464
Ettinger L, Ru N, Krailo M, Ruccione K, Krivit W, Hammond G (1990) A phase II study of diaziquone in children with recurrent or progressive primary brain tumors: a report from the Children’s Cancer Study Group. J Neurooncol 9:69–76
Ewend M, Sampath P, Williams J, Tyler B, Brem H (1998) Local delivery of chemotherapy prolongs survival in experimental brain metastases from breast carcinoma. Neurosurgery 43:1185–1193
Fleischhack G, Jaehde U, Bode U (2005) Pharmacokinetics following intraventricular administration of chemotherapy in patients with neoplastic meningitis. Clin Pharmacokinet 4:1–31
Friedman H (2000) Temozolomide in early stages of newly diagnosed malignant glioma and neoplastic meningitis. Semin Oncol 27:35–40
Friedman H, Bigner S, Bigner D (1995) Cyclophosphamide therapy of medulloblastoma: from the laboratory to the clinic and back again (and again and again). J Neurooncol 24:103–108
Friedman H, Ochs J, Finlay J, Geyer R, Arndt C, Cohen B, Phillips P, Strauss L, Hochberg F, Schold S, Bigner D, Colvin O (1993) Phase I trial of intrathecal 4-hydroperoxycyclophosphamide for neoplastic meningitis. American Association for Cancer Research. p 269
Green L (1988) Choice of diluents for intrathecal drug administration. Clin Pharmacy 7:265–266
Grill J, Sainte-Rose C, Jouvet A, Gentet J-C, Lejars O, Frappaz D, Doz F, Rialland X, Pichon F, Bertozzi A-I, Chastagner P, Couanet D, Habrand J-L, Raquin M-A, Le Deley M-C, Kalifa C (2005) Treatment of medulloblastoma with postoperative chemotherapy alone: an SFOP prospective trial in young children. Lancet Oncol 6:573–580
Grossman S, Trump DL, Chen D, Thompson G, Camargo E (1982) Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using 111Indium DTPA ventriculography. Am J Med 73:641–647
Gururangan S, Petros W, Young Poussaint T, Hancock M, Phillips P, Friedman H, Bomgaars L, Blaney S, Kun L, Boyett J (2006) 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
Gutman R, Peacock G, Lu D (2000) Targeted drug delivery for brain cancer treatment. J Controlled Release 65:31–41
Haberler C, Varlet P, Legoix P, Fattet S, Janoueix-Lerosey I, Lellouch-Tubiana A, Grill J, Doz F, Sainte-Rose C, Delattre O (2008) Widespread nuclear beta-catenin expression in medulloblastoma correlates with mutation status of CTNNB1 gene encoding beta-catenin. Neurooncology 10:470
Hare C, Elion G, Houghton P, Houghton J, Keir S, Marcelli S, Bigner D, Friedman H (1997) Therapeutic efficacy of the topoisomerase I inhibitor 7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptothecin against pediatric and adult central nervous system tumor xenografts. Cancer Chemother Pharmacol 39:187–191
Heideman RL, McCully C, Balis F, Poplack D (1993) Cerebrospinal fluid pharmacokinetics and toxicology of intraventricular and intrathecal arabinosyl-5-azacytosine (fazarabine, NSC 281272) in the nonhuman primate. Investig New Drugs 11:135–140
Hori T, Tanaka S, Nishiyama M, Kamitani H, Watanabe T, Tabuchi F, Tatsuhara T, Nakajima E (1993) Distribution of intrathecally administered ACNU in mongrel dogs: pharmacokinetics and quantitative autoradiographic study. Surg Neurol 40:183–195
Houchens D, Ovejera A, Riblet S, Slagel D (1983) Human brain tumor xenografts in nude mice as a chemotherapy model. Eur J Cancer Clin Oncol 19:799–805
Huang T-Y, Howng S-L (1997) Intrathecal ACNU against experimental leptomeningeal tumors. Kaohsiung J Med Sci 13:626–630
Hussain M, Wozniak A, Edelstein M (1993) Neurotoxicity of antineoplastic agents. Crit Rev Oncol Hematol 14:61–75
Jabbour E, O’Brien S, Kantarjian H, Garcia-Manero G, Ferrajoli A, Ravandi F, Cabanillas M, Thomas DA (2007) Neurologic complications associated with intrathecal liposomal cytarabine given prophylactically in combination with high-dose methotrexate and cytarabine to patients with acute lymphocytic leukemia. Blood 109:3214–3218
Jaeckle K, Batchelor T, O’Day S, Phuphanich S, New P, Lesser G, Cohn A, Gilbert M, Aiken R, Heros D, Rogers L, Wong E, Fulton D, Gutheil J, Baidas S, Kennedy J, Mason W, Moots P, Russell C, Swinnen L, Howell S (2002) An open label trial of sustained-release cytarabine (DepoCyt) for the intrathecal treatment of solid tumor neoplastic meningitis. J Neurooncol 57:231–239
Kerr J, Berg S, Dauser R, Nuchtern J, Egorin M, McGuffey L, Aleksic A, Blaney S (2001) Plasma and cerebrospinal fluid pharmacokinetics. Cancer Chemother Pharmacol 47:411–414
Kim S, Chatelut E, Kim J, Howell S, Cates C, Kormanik P, Chamberlain M (1993) Extended CSF cytarabine exposure following intrathecal administration of DTC 101. J Clin Oncol 11:2186–2193
Kim S, Khatibi S, Howell S, McCully C, Balis F, Poplack D (1993) Prolongation of drug exposure in cerebrospinal fluid by encapsulation into DepoFoam. Cancer Res 53:1596–1598
Kim S, Kim D, Geyer M, Howell S (1987) Multivesicular liposomes containing 1-β-d-arabinofuranosylcytosine for slow-release intrathecal therapy. Cancer Res 47:3935–3937
Kimler B, Liu C, Evans R, Morantz R (1992) Intracerebral chemotherapy in the 9L rat brain tumor model. J Neurooncol 14:191–200
Kitamura I, Kochi M, Matsumoto Y, Ueoka R, Kuratsu J-I, Ushio Y (1996) Intrathecal chemotherapy with 1, 3-bis(2-chloroethyl)-1-nitrosourea encapsulated into hybrid liposomes for meningeal gliomatosis: an experimental study. Cancer Res 56:3986–3992
Kleinschmidt-DeMasters B, Yeh M (1992) “Locked-in syndrome” after intrathecal cytosine arabinoside therapy for malignant immunoblastic lymphoma. Cancer 70:2504–2507
Kochi M, Kuratsu J-I, Mihara Y, Takaki S, Inoue N, Sueyoshi N, Uemura S, Ushio Y (1990) Neurotoxicity and pharmacokinetics of intrathecal perfusion of ACNU in dogs. Cancer Res 50:3119–3123
Kochi M, Kuratsu J-I, Mihara Y, Takaki S, Seto H, Uemura S, Ushio Y (1993) Ventriculolumbar perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(chloroethyl)-1-nitrosourea hydrochloride. Neurosurgery 33:817–823
Kochi M, Takaki S, Kuratsu J-I, Seto H, Kitamura I, Ushio Y (1994) Neurotoxicity and pharmacokinetics of ventriculolumbar perfusion of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-d-gluco-pyranoside (MCNU) in dogs. J Neurooncol 19:239–244
Kohn F, Malkmus S, Brownson E, Rossi S, Yaksh T (1998) Fate of the predominant phospholipid component of DepoFoam™ drug delivery matrix after intrathecal administration of sustained-release encapsulated cytarabine in rats. Drug Deliv 5:143–151
Kooistra K, Rodriguez M, Powis G (1989) Toxicity of intrathecally administered cytotoxic drugs and their antitumor activity against an intrathecal Walker 256 carcinosarcoma model for meningeal carcinomatosis in the rat. Cancer Res 49:977–982
Kreuter J (2001) Nanoparticulate systems for brain delivery of drugs. Adv Drug Deliv Rev 47:65–81
Kuhl J, Doz F, Taylor R (2004) Embryonic tumors. In: Walker D, Perilongo G, Punt J, Taylor R (eds) Brain and spinal tumors of childhood. Arnold, London, pp 314–330
Lassaletta A, Lopez-Ibor B, Mateos E, Gonzalez-Vicent M, Perez-Martinez A, Sevilla J, Diaz M, Madero L (2009) Intrathecal liposomal cytarabine in children under 4 years with malignant brian tumours. J Neurooncology (in press)
Levin V, Byrd D, Sikic B, Etiz B, Campbell J, Borcich J, Davis R (1985) Central nervous system toxicity and cerebrospinal fluid pharmacokinetics of intraventricularly administered bleomycin in beagles. Cancer Res 45:3810–3815
Levin V, Chamberlain M, Silver P, Rodriguez L, Prados M (1989) Phase I/II study of intraventricular and intrathecal ACNU for leptomeningeal neoplasia. Cancer Chemother Pharmacol 23:301–307
Levin V, Edwards M, Gutin P, Vestnys P, Fulton D, Seager M, Wilson C (1984) Phase II evaluation of dibromodulcitol in the treatment of recurrent medulloblastoma, ependymoma and malignant astrocytoma. J Neurosurg 61:1063–1068
Lind M (1993) Pharmacokinetics of alkylating agents. Pharmacokinet Cancer Chemother 17:157–179
MacDonald D (1991) Neurologic complications of chemotherapy. Neurol Clin 9:955–967
Martindale (1999) The complete drug reference. Pharmaceutical Press, London
McKeran R, Firth G, Oliver S, Uttley D, O’Laoire S (1985) A potential application for the intracerebral injection of drugs entrapped within liposomes in the treatment of human cerebral gliomas. J Neurol Neurosurg Psychiatry 48:1213–1219
McVie J (1992) Teniposide (VM-26) in brain tumors. Semin Oncol 19:85–88
Morantz R, Kimler B, Vats T, Henderson S (1983) Leomycin and brain tumors. J Neurooncol 1:249–255
Nakagawa H, Maeda N, Tsuzuki T, Suzuki T, Hirayama A, Miyahara E, Wada K (2001) Intracavitary chemotherapy with 5-fluoro-2′-deoxyuridine (FdUrd) in malignant brain tumors. Jpn J Clin Oncol 31:251–258
Nakagawa H, Miyahara E, Suzuki T, Wada K, Tamura M, Fukushima Y (2005) Continuous intrathecal administration of 5-fluoro-2′-deoxyuridine for the treatment of neoplastic meningitis. Neurosurgery 57:266–280
Nakagawa H, Yamada M, Fukushima M, Ikenaka K (1999) Intrathecal 5-fluoro-2′-deoxyuridine (FdUrd) for the treatment of solid tumor neoplastic meningitis: an in vivo study. Cancer Chemother Pharmacol 43:247–256
Nakagawa H, Yamada M, Maeda N, Iwatsuki K, Hirayama Z, Ikenaka K (1999) Clinical trial of intrathecal administration of 5-fluoro-2′-deoxyuridine for treatment of meningeal dissemination of malignant brain tumors. J Neurooncol 45:175–183
National Cancer Institute. http://www.nci.nih.gov
National Library of Medicine Special Information Services. http://chem.sis.nlm.nih.gov
Newlands E, Stevens M, Wedge S, Wheelhouse R, Brock C (1997) Temozolomide: a review of its discovery, chemical properties, pre-clinical development and clinical trials. Cancer Treat Rev 23:35–61
Nishio S, Morioka T, Takeshita I, Tadahisa S, Takanori I, Fujiwara S, Fukui M (1995) Chemotherapy for progressive pilocytic astrocytomas in the chiasmo-hypothalamic regions. Clin Neurol Neurosurg 87:300–306
Ochiai H, Pernell C, Archer G, Chewning T, McLendon R, Friedman H, Sampson J (2006) Treatment of neoplastic meningitis with intrathecal 9-nitro-camptothecin. Neurol Med Chir (Tokyo) 46:485–490
Olivi A, Dundan L, Corden B, Lenartz D, Brem H (1993) Direct delivery of platinum based neoplastics to the central nervous system : a toxicity and ultrastructural study. Cancer Chemotherapy Pharmacol 31:449–454
Paal C, Erdelyi-Toth V, Pap E, Csaki C, Ferencz T, Schuler D, Borsi J (1994) Pharmacokinetic studies on Elobromol in children with brain tumors. Anti-Cancer Drugs 5:539–547
Pardridge W (1996) Brain drug delivery and blood–brain barrier transport. Drug Deliv 3:99–115
Pardridge W (2002) Drug and gene targeting to the brain with molecular Trojan horses. Nat Rev Drug Discov 1:131–139
Perry J, Chambers A, Spithoff K, Laperriere N (2007) Gliadel wafers in the treatment of malignant glioma: a systematic review. Curr Oncol 14(5):189–194
Phillips P, Than T, Cork L, Hilton J, Carson B, Colvin O, Grochow L (1992) Intrathecal 4-hydroperoxycyclophosphamide: neurotoxicity, cerebrospinal fluid pharmacokinetics, and antitumor activity in a rabbit model of VX2 leptomeningeal carcinomatosis. Cancer Res 52:6168–6174
Read T-A, Thorsen F, Bjerkvig R (2002) Localised delivery of therapeutic agents to CNS malignancies; old and new approaches. Curr Pharm Technol 3:257–273
Rhone Poulenc Rorer (1999) Information from medical information department. West Malling, Kent
Riccardi R, Riccardi A, Di Rocco C, Carelli G, Tartaglia R, Lasorella A, Servidei T, Mastrangelo R (1992) Cerebrospinal fluid pharmacokinetics of carboplatin in children with brain tumors. Cancer Chemother Pharmacol 30:21–24
Ruggiero A, Conter V, Milani M, Biagi E, Lazzareschi I, Sparano P, Riccardi R (2001) Intrathecal chemotherapy with antineoplastic agents in children. Paediatr Drugs 3:237–246
Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, Graf N, Emser A, Pietsch T, Wolff J, Korkmann R, Kuehl J (2005) Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med 352:978–986
Rutkowski S, Von Hoff K, Emser A, Garre ML, Walker D, Grundy R, Dhall G, Finlay J, Grill J (2008) Prognostic factors and survival of young children with medulloblastoma: an international meta-analysis. Neurooncology 10:437
Sampson J, Archer G, Villavicencio A, McLendon R, Friedman A, Bishop W, Bigner D, Friedman H (1999) Treatment of neoplastic meningitis with intrathecal temozolomide. Clin Cancer Res 5:1183–1188
Savaraj N, Feun L, Lu K, Gray K, Wang C, Loo T (1992) Pharmacology of intrathecal VP-16-213 in dogs. J Neurooncol 13:211–215
Savas A, Erdem A, Tun K, Kanpolat Y (2000) Fatal toxic effect of bleomycin in brain tissue after intracystic chemotherapy for a craniopharyngioma: case report. Neurosurgery 46:213–217
Schmandt S, Kuhl J (1998) Chemotherapy as prophylaxis and treatment of meningosis in children less than 3 years of age with medulloblastoma. J Neurooncol 38:187–192
Schold S Jr, Mahaley M Jr, Vick N, Friedman H, Burger P, DeLong E, Albright R Jr, Bullard D, Khandekar D, Cairncross J, Macdonald D, Falletta J (1987) Phase II diaziquone-based chemotherapy trials in patients with anaplastic supratentorial astrocytic neoplasms. J Clin Oncol 5:464–471
Schuler D, Somlo P, Borsi J, Paraicz E, Revesz T, Kardos G, Koos R (1988) New drug combination for the treatment of relapsed brain tumors in children. Pediatr Hematol Oncol 5:153–156
Schuler D, Somlo P, Koos R, Kalmanchey R, Paraicz E (1992) Treatment of malignant scala posterior brain tumors in children: the chemotherapy of relapsed medulloblastoma with a dibromdulcitol-containing drug regime and pharmacokinetic studies of dibromdulcitol in children. Med Pediatr Oncol 20:312–314
Screnci D, McKeage M, Galettis P, Hambley T, Palmer B, Baguley B (2000) Relationships between hydrophobicity, reactivity, accumulation and peripheral nerve toxicity of a series of platinum drugs. Br J Cancer 82:966–972
Selby G, Upchurch C, Townsend J, Eyre H (1994) A phase II evaluation of fazarabine in high-grade gliomas: a Southwest Oncology Group study. Cancer Chemother Pharmacol 34:179–180
Slavc I, Schuller E, Czech T, Hainfellner J, Seidl R, Dieckmann K (1998) Intrathecal mafosfamide therapy for paediatric brain tumors with meningeal dissemination. J Neurooncol 38:213–218
Slavc I, Schuller E, Falger J, Gunes M, Pillwein K, Czech T, Dietrich W, Rossler K, Dieckmann K, Prayer D, Hainfellner J (2003) Feasibility of long-tem intraventricular therapy with mafosfamide (n = 26) and etoposide (n = 11): experience in 26 children with disseminated malignant brain tumors. J Neurooncol 64:239–247
SmithKline Beecham Pharmaceuticals (1999) Information from medical information department. Welwyn Garden City
Stempien L, Tsai T (2000) Intrathecal baclofen pump use for spasticity: a clinical survey. Am J Phys Med Rehabil 79:536–541
Stevens M, Newlands E (1993) From triazines and triazines to temozolomide. Eur J Cancer 29a:1045–1047
Stiller C, Bleyer W (2004) Epidemiology. In: Walker D, Perilongo G, Punt J, Taylor R (eds) Brain and spinal tumors of childhood. Arnold, London, pp 35–49
Taylor E (2002) The impact of efflux transporters in the brain on the development of drugs for CNS disorders. Clin Pharmacokinet 41:81–92
Taylor S (1994) New agents in the treatment of primary brain tumors. J Neurooncol 20:141–153
Tomlinson F, Lihou M, Smith P (1991) Comparison of in vitro activity of epipodophyllotoxins with other chemotherapeutic agents in human medulloblastomas. Br J Cancer 64:1051–1059
Tsuboi K, Yoshii Y, Hyodo A, Takada K, Nose T (1995) Leukoencephalopathy associated with intra-arterial ACNU in patients with gliomas. J Neurooncol 23:223–231
Tuxen M, Hansen S (1994) Neurotoxicity secondary to antineoplastic drugs. Cancer Treat Rev 20:191–214
Ushio Y, Kochi M (1998) Intrathecal perfusion chemotherapy with ACNU against subarachnoid dissemination of glioma in children. Int J Pediat Hem Oncol 5:55–56
Ushio Y, Kochi M, Kitamura I, Kuratsu J (1998) Ventriculolumbar perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)-methyl]-1-(2-cloroethyl)-1-nitrosourea hydrochloride for subarachnoid dissemination of gliomas. J Neurooncol 38:207–212
van der Gaast A, Sonneveld P, Mans D, Splinter T (1992) Intrathecal administration of etoposide in the treatment of malignant meningitis: feasibility and pharmacokinetic data. Cancer Chemother Pharmacol 29:335–337
van der Graaf W, Haaxma-Reiche H, Burghouts J, Postmus P (1993) Teniposide for meningeal carcinomatosis of small cell lung cancer. Lung Cancer 10:247–249
Vassal G, Boland I, Santos A, Bissery M, Terrier-Lacombe M, Morizet J, Sainte-Rose C, Lellouch-Tubiana A, Kalifa C, Gouyette A (1997) Potent therapeutic activity of irinotecan (CPT-11) and its schedule dependency in medulloblastoma xenografts in nude mice. Int J Cancer 73:156–163
Vassal G, Boland I, Terrier-Lacombe M, Watson A, Margison G, Venuat A, Morizet J, Parker F, Lacroix C, Lellouch-Tubiana A, Pierre-Kahn A, Poullain M, Gouyette A (1998) Activity of fotemustine in medulloblastoma and malignant glioma xenografts in relation to O 6-alkylguanine-DNA alkyltransferase and alkylpurine-DNA N-glycosylase activity. Clin Cancer Res 4:463–468
Vassal G, Pondarre C, Boland I, Cappelli C, Santos A, Thomas C, Lucchi E, Imadalou K, Pein F, Morizet J, Gouyette A (1998) Preclinical development of camptothecin derivatives and clinical trials in pediatric oncology. Biochimie 80:271–280
Vassal G, Terrier-Lacombe M-J, Bissery M, Venuat A, Gyergyay F, Benard J, Morizet J, Boland I, Ardouin P, Bressac-de-Paillerets B, Gouyette A (1996) Therapeutic activity of CPT-11, a DNA-topoisomerase I inhibitor, against peripheral primitive neuroectodermal tumour and neuroblastoma xenografts. Br J Cancer 75:537–545
Walker D, Wilne S (2005) Treatment of medulloblastoma in young children. Lancet Oncol 6:541–542
Wang P, Frazier J, Brem H (2002) Local drug delivery to the brain. Adv Drug Deliv 54:987–1013
Ward H (1978) Central nervous system tumors of childhood treated with CCNU, vincristine and radiation. Med Pediatr Oncol 4:315–320
Watterson J, Toogood I, Nieder M, Morse M, Frierdich S, Lee Y, Moertel C, Priest J (1994) Excessive spinal cord toxicity from intensive central nervous system-directed therapies. Cancer 74:3034–3041
Weiss R, Issell B (1982) The nitrosoureas: carmustine (BCNU) and lomustine (CCNU). Cancer Treat Rev 9:313–330
Westphal M, Ram Z, Riddle V, Hilt D, Bortey E (2006) Gliadel® wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial. Acta Neurochir 148:269–275
Yamada M, Nakagawa H, Fukushima M, Shimizu K, Hayakawa T, Ikenaka K (1998) In vitro study on intrathecal use of 5-fluoro-2′-deoxyuridine (FdUrd) for meningeal dissemination of malignant brain tumors. J Neurooncol 37:115–121
Yamasaki T, Kikuchi H, Yamashita J, Asato R, Fujita M (1989) Primary spinal intramedullary malignant melanoma: case report. Neurosurgery 25:117–121
Yamashima T, Yamashita J, Shoin K (1990) Neurotoxicity of local administration of two nitrosoureas in malignant gliomas. Neurosurgery 26:794–800
Yoshida T, Beuls E, Shimizu K, Koulousakis A, Sturm V (1992) Intrathecal chemotherapy with ACNU for meningeal gliomatosis. Br J Cancer 66:999–1004
Yoshida T, Shimizu K, Koulousakis A, Sturm V (1992) Intrathecal chemotherapy with ACNU in a meningeal gliomatosis rat model. J Neurosurg 77:778–782
Yoshimura J, Nishiyama K, Mori H, Takahashi H, Fujii Y (2008) Intrathecal chemotherapy for refractory disseminated medulloblastoma. Child’s Nerv Syst 24:581–585
Zimm S, Collins J, Curt G, O’Neill D, Poplack D (1984) Cerebrospinal fluid pharmacokinetics of intraventricular and intravenous aziridinylbenzoquinone. Cancer Res 44:1698–1701
Zimm S, Collins J, Miser J, Chatterji D, Poplack D (1984) Cytosine arabinoside cerebrospinal fluid kinetics. Clin Pharmacol Therap 35:826–830
Acknowledgments
This work has been supported by funding from the Children’s Brain Tumour Research Centre at the University of Nottingham. The authors would like to acknowledge the assistance of Professor Imti Choonara in the development of strategy and review of the manuscript, Steve Barrett in the conduct of the literature searching and Sue Franklin in the preparation of the manuscript.
Conflict of interest statement
There are no conflicts of interest to declare. This work was conducted without any financial assistance outside of the University of Nottingham.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Conroy, S., Garnett, M., Vloeberghs, M. et al. Medulloblastoma in childhood: revisiting intrathecal therapy in infants and children. Cancer Chemother Pharmacol 65, 1173–1189 (2010). https://doi.org/10.1007/s00280-009-1127-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00280-009-1127-1