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Intraarterial drug delivery for glioblastoma mutiforme

Will the phoenix rise again?

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Abstract

Intraarterial (IA) drug delivery is a physiologically appealing strategy as drugs are widely distributed throughout the tumor capillary network and high regional tissue concentrations can be achieved with low total doses. IA treatment of glioblastoma multiforme (GBM) has been attempted since the 1950s but success has been elusive. Although IA treatments have been embraced for the treatment of retinoblastoma and advanced liver cancers, this has not been the case for GBM. The development of IA drug delivery for the treatment of brain cancer over the last several decades reveals a number of critical oversights. For example, very few studies took into consideration the underlying hydrodynamic factors. Therapeutic failures were often blamed on an inability to penetrate the blood brain barrier or on the streaming of drugs. Similarly, there were few methods to investigate the ultra-fast pharmacokinetics of IA drugs. Despite past failures, clinical interest in IA drugs for the treatment of GBM persists. The advent of modern imaging methods along with a better understanding of hydrodynamics factors, better appreciation of the complex morphology of GBM, improved drug selection and formulations, and development of methods to minimize treatment-related neurological injury, promise to considerably advance the application of IA drugs for GBM treatment. There are several clinical trials with IA treatments in the National Trial Registry that are actively recruiting patients. This review of IA drug delivery for GBM treatment is therefore timely and is intended to assess how this method of drug delivery could be better applied to future treatments.

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References

  1. Einhorn J (1985) Nitrogen mustard: the origin of chemotherapy for cancer. Inter J Radiat Oncol, Biol, Phys 11(7):1375–1378

    Article  CAS  Google Scholar 

  2. Klopp CT, Alford TC, Bateman J, Berry GN, Winship T (1950) Fractionated intra-arterial cancer; chemotherapy with methyl bis amine hydrochloride; a preliminary report. Ann Surg 132(4):811–832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Wilson CB (1964) Chemotherapy of Brain Tumors by Continuous Arterial Infusion. Surgery 55:640–653

    CAS  PubMed  Google Scholar 

  4. Rapoport SI, Hori M, Klatzo I (1971) Reversible osmotic opening of the blood-brain barrier. Science 173(4001):1026–1028

    Article  CAS  PubMed  Google Scholar 

  5. Oldfield EH, Clark WC, Dedrick RL, Egorin MJ, Austin HA, DeVroom HD, Joyce KM, Doppman JL (1987) Reduced systemic drug exposure by combining intraarterial cis-diamminedichloroplatinum(II) with hemodialysis of regional venous drainage. Cancer Res 47(7):1962–1967

    CAS  PubMed  Google Scholar 

  6. Dedrick RL (1988) Arterial drug infusion: pharmacokinetic problems and pitfalls. J Nat Cancer Inst 80(2):84–89

    Article  CAS  PubMed  Google Scholar 

  7. Neuwelt E, Abbott NJ, Abrey L, Banks WA, Blakley B, Davis T, Engelhardt B, Grammas P, Nedergaard M, Nutt J, Pardridge W, Rosenberg GA, Smith Q, Drewes LR (2008) Strategies to advance translational research into brain barriers. Lancet Neurol 7(1):84–96

    Article  CAS  PubMed  Google Scholar 

  8. Bigio IJ, Bown SG (2004) Spectroscopic sensing of cancer and cancer therapy: current status of translational research. Cancer Biol Ther 3(3):259–267

    Article  CAS  PubMed  Google Scholar 

  9. Joshi S, Meyers PM, Ornstein E (2008) Intracarotid delivery of drugs: the potential and the pitfalls. Anesthesiology 109(3):543–564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Francis JH, Gobin YP, Brodie SE, Marr BP, Dunkel IJ, Abramson DH (2012) Experience of intra-arterial chemosurgery with single agent carboplatin for retinoblastoma. British J Ophthalmol 96(9):1270–1271. doi:10.1136/bjophthalmol-2012-301686

    Article  Google Scholar 

  11. Nakasato T, Katoh K, Sone M, Ehara S, Tamakawa Y, Hoshi H, Sekiyama S (2000) Superselective continuous arterial infusion chemotherapy through the superficial temporal artery for oral cavity tumors. AJNR Am J Neuroradiol 21(10):1917–1922

    CAS  PubMed  Google Scholar 

  12. Cristina V, Pracht M, Lachenal Y, Adib S, Boubaker A, Prior J, Senys A, Wagner AD, Bize P (2014) [Interventional radiology procedures for malignancies of the liver treatment: Intraarterial procedures]. Revue medicale suisse 10 (431):1130–1132, 1134–1135

  13. Rashid OM, Sloot S, Zager JS (2014) Regional therapy in metastatic melanoma: an update on minimally invasive intraarterial isolated limb infusion and percutaneous hepatic perfusion. Expert Opin Drug Metab Toxicol 10:1–10. doi:10.1517/17425255.2014.951330

    Article  Google Scholar 

  14. Wang X, Gan C, Li H, Wei Y, Zhu D, Yang G, Su X, Rodier JF, Ren G (2013) Main complications and results of treatment with intra-arterial infusion chemotherapy through the subclavian and thoracic arteries for locally advanced breast cancer. Mol Clin Oncol 1(4):745–748. doi:10.3892/mco.2013.129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Homma H, Doi T, Mezawa S, Takada K, Kukitsu T, Oku T, Akiyama T, Kusakabe T, Miyanishi K, Niitsu Y (2000) A novel arterial infusion chemotherapy for the treatment of patients with advanced pancreatic carcinoma after vascular supply distribution via superselective embolization. Cancer 89(2):303–313

    Article  CAS  PubMed  Google Scholar 

  16. Chiang PH, Chen CH, Shen YC (2014) Intraarterial chemotherapy as the first-line therapy in penile cancer. British J Cancer 111(6):1089–1094. doi:10.1038/bjc.2014.394

    Article  CAS  Google Scholar 

  17. Jiang L, Zhang Z, Dong P, Li Y, Yao K, Liu Z, Han H, Qin Z, Yao M, Zhou F (2014) Efficacy of radical cystectomy plus adjuvant intraarterial chemotherapy with gemcitabine and cisplatin on locally advanced bladder cancer. Chin Med J 127(7):1249–1254

    PubMed  Google Scholar 

  18. Stratmann SL (2002) Hepatic artery chemotherapy in the management of colorectal metastases. Proceedings 15 (4):376–379

  19. Tyler JL, Yamamoto YL, Diksic M, Theron J, Villemure JG, Worthington C, Evans AC, Feindel W (1986) Pharmacokinetics of superselective intra-arterial and intravenous [11C]BCNU evaluated by PET. J Nucl Med 27(6):775–780

    CAS  PubMed  Google Scholar 

  20. Joshi S, Wang M, Etu JJ, Suckow RF, Cooper TB, Feinmark SJ, Bruce JN, Fine RL (2007) Transient cerebral hypoperfusion enhances intraarterial carmustine deposition into brain tissue. J Neurooncol 86:123–132

    Article  PubMed  Google Scholar 

  21. Joshi S, Wang M, Etu JJ, Nishanian EV, Pile-Spellman J (2006) Cerebral blood flow affects dose requirements of intracarotid propofol for electrocerebral silence. Anesthesiology 104(2):290–298

    Article  CAS  PubMed  Google Scholar 

  22. Joshi S, Singh-Moon RP, Ellis JA, Chaudhuri DB, Wang M, Reif R, Bruce JN, Bigio IJ, Straubinger RM (2014) Cerebral Hypoperfusion-assisted Intraarterial Deposition of Liposomes in Normal and Glioma-bearing Rats. Neurosurgery NIHMS 624641 (in press)

  23. Joshi S, Singh-Moon RP, Wang M, Chaudhuri DB, Holcomb M, Straubinger NL, Bruce JN, Bigio IJ, Straubinger RM (2014) Transient cerebral hypoperfusion assisted intra-arterial cationic liposome delivery to brain tissue. J Neurooncol. doi:10.1007/s11060-014-1421-6

    Google Scholar 

  24. Stephens FO (1995) Induction (neo-adjuvant) chemotherapy: systemic and arterial delivery techniques and their clinical applications. Aust New Zealand J Surg 65(10):699–707

    Article  CAS  Google Scholar 

  25. Yamane T, Kaneko A, Mohri M (2004) The technique of ophthalmic arterial infusion therapy for patients with intraocular retinoblastoma. Intern J Clin Oncol 9(2):69–73. doi:10.1007/s10147-004-0392-6

    Article  Google Scholar 

  26. Boas DA, Frostig RD (2005) Optics in neuroscience. J Biomed Opt 10(1):1–2

    Article  Google Scholar 

  27. Reif R, Wang M, Joshi S, A’Amar O, Bigio IJ (2007) Optical method for real-time monitoring of drug concentrations facilitates the development of novel methods for drug delivery to brain tissue. J Biomed Opt 12(3):034036

    Article  PubMed  Google Scholar 

  28. Dedrick RL, Oldfield EH, Collins JM (1984) Arterial drug infusion with extracorporeal removal. I. Theoretic basis with particular reference to the brain. Cancer Treat Rep 68(2):373–380

    CAS  PubMed  Google Scholar 

  29. Doolittle ND, Muldoon LL, Culp AY, Neuwelt EA (2014) Delivery of chemotherapeutics across the blood-brain barrier: challenges and advances. Adv Pharmacol 71:203–243. doi:10.1016/bs.apha.2014.06.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Yuan F, Salehi HA, Boucher Y, Vasthare US, Tuma RF, Jain RK (1994) Vascular permeability and microcirculation of gliomas and mammary carcinomas transplanted in rat and mouse cranial windows. Cancer Res 54(17):4564–4568

    CAS  PubMed  Google Scholar 

  31. Hossain SS, Hughes TJ, Decuzzi P (2013) Vascular deposition patterns for nanoparticles in an inflamed patient-specific arterial tree. Biomech Model Mechanobiol. doi:10.1007/s10237-013-0520-1

    PubMed  PubMed Central  Google Scholar 

  32. Agid R, Rubinstein R, Siegal T, Lester H, Bokstein F, Chisin R, Gomori JM (2002) Does streaming affect the cerebral distribution of infraophthalmic intracarotid chemotherapy? AJNR. American Journal of Neuroradiology 23(10):1732–1735

    PubMed  Google Scholar 

  33. Liu Y, Shah S, Tan J (2012) Computational modeling of nanoparticle targeted drug delivery. Rev Nanosci Nanotech 1:66–83

    Article  CAS  Google Scholar 

  34. Boockvar JA, Tsiouris AJ, Hofstetter CP, Kovanlikaya I, Fralin S, Kesavabhotla K, Seedial SM, Pannullo SC, Schwartz TH, Stieg P, Zimmerman RD, Knopman J, Scheff RJ, Christos P, Vallabhajosula S, Riina HA (2011) Safety and maximum tolerated dose of superselective intraarterial cerebral infusion of bevacizumab after osmotic blood-brain barrier disruption for recurrent malignant glioma Clinical article. Journal of Neurosurgery 114(3):624–632. doi:10.3171/2010.9.Jns101223

    Article  CAS  PubMed  Google Scholar 

  35. Chow KL, Gobin YP, Cloughesy T, Sayre JW, Villablanca JP, Vinuela F (2000) Prognostic factors in recurrent glioblastoma multiforme and anaplastic astrocytoma treated with selective intra-arterial chemotherapy. AJNR Am J Neuroradiol 21(3):471–478

    CAS  PubMed  Google Scholar 

  36. Fortin D, Desjardins A, Benko A, Niyonsega T, Boudrias M (2005) Enhanced chemotherapy delivery by intraarterial infusion and blood-brain barrier disruption in malignant brain tumors: the Sherbrooke experience. Cancer 103(12):2606–2615

    Article  PubMed  Google Scholar 

  37. Fortin D, Morin PA, Belzile F, Mathieu D, Pare FM (2014) Intra-arterial carboplatin as a salvage strategy in the treatment of recurrent glioblastoma multiforme. J Neurooncol 119(2):397–403. doi:10.1007/s11060-014-1504-4

    Article  CAS  PubMed  Google Scholar 

  38. Gobin YP, Cloughesy TF, Chow KL, Duckwiler GR, Sayre JW, Milanese K, Vinuela F (2001) Intraarterial chemotherapy for brain tumors by using a spatial dose fractionation algorithm and pulsatile delivery. Radiology 218(3):724–732

    Article  CAS  PubMed  Google Scholar 

  39. Imbesi FME, Benericetti E, Zappoli F, Galli A, Corato M, Ceroni M (2006) A randomized phase III study: comparison between intravenous and intraarterial ACNU administration in newly diagnosed primary glioblastomas. Anticancer Res 26(1B):553–558

    CAS  PubMed  Google Scholar 

  40. Qureshi AI, Suri MF, Khan J, Sharma M, Olson K, Guterman LR, Hopkins LN (2001) Superselective intra-arterial carboplatin for treatment of intracranial neoplasms: experience in 100 procedures. J Neurooncol 51(2):151–158

    Article  CAS  PubMed  Google Scholar 

  41. Shin BJ, Burkhardt JK, Riina HA, Boockvar JA (2012) Superselective intra-arterial cerebral infusion of novel agents after blood-brain disruption for the treatment of recurrent glioblastoma multiforme: a technical case series. Neurosurg Clin N Am 23(2):323–329 ix-x

    Article  PubMed  Google Scholar 

  42. Jeon JY, Kovanlikaya I, Boockvar JA, Mao X, Shin B, Burkhardt K, Kesavabhotla K, Christos P, Riina H, Shungu DC, Tsiouris AJ (2012) Metabolic response of glioblastoma to superselective intra-arterial cerebral infusion of bevacizumab: a proton MR spectroscopic imaging study. AJNR Am J Neuroradiol 33(11):2095–2102. doi:10.3174/ajnr.A3091

    Article  CAS  PubMed  Google Scholar 

  43. Hall WA, Doolittle ND, Daman M, Bruns PK, Muldoon L, Fortin D, Neuwelt EA (2006) Osmotic blood-brain barrier disruption chemotherapy for diffuse pontine gliomas. J Neurooncol 77(3):279–284. doi:10.1007/s11060-005-9038-4

    Article  CAS  PubMed  Google Scholar 

  44. Peschillo S, Miscusi M, Missori P (2015) Endovascular superselective treatment of brain tumors: a new endovascular era? A quick review. J Neurointerv Surg 7(3):222–224. doi:10.1136/neurintsurg-2013-011095

    Article  PubMed  Google Scholar 

  45. Newton HB (2012) Neurological complications of chemotherapy to the central nervous system. Handbook Clin Neurol 105:903–916. doi:10.1016/B978-0-444-53502-3.00031-8

    Article  Google Scholar 

  46. Elkassabany NM, Bhatia J, Deogaonkar A, Barnett GH, Lotto M, Maurtua M, Ebrahim Z, Schubert A, Ference S, Farag E (2008) Perioperative complications of blood brain barrier disruption under general anesthesia: a retrospective review. J Neurosurg Anesthesiol 20(1):45–48

    Article  PubMed  Google Scholar 

  47. Zylber-Katz E, Gomori JM, Schwartz A, Lossos A, Bokstein F, Siegal T (2000) Pharmacokinetics of methotrexate in cerebrospinal fluid and serum after osmotic blood-brain barrier disruption in patients with brain lymphoma. Clin Pharmacol Ther 67(6):631–641

    Article  CAS  PubMed  Google Scholar 

  48. Doolittle ND, Miner ME, Hall WA, Siegal T, Jerome E, Osztie E, McAllister LD, Bubalo JS, Kraemer DF, Fortin D, Nixon R, Muldoon LL, Neuwelt EA (2000) Safety and efficacy of a multicenter study using intraarterial chemotherapy in conjunction with osmotic opening of the blood-brain barrier for the treatment of patients with malignant brain tumors. Cancer 88(3):637–647

    Article  CAS  PubMed  Google Scholar 

  49. Riina HA, Knopman J, Greenfield JP, Fralin S, Gobin YP, Tsiouris AJ, Souweidane MM, Boockvar JA (2010) Balloon-assisted superselective intra-arterial cerebral infusion of bevacizumab for malignant brainstem glioma. A technical note. Interv Neuroradiol: J Peritherapeutic Neuroradiol, Surg Proc Related Neurosci 16(1):71–76

    Article  CAS  Google Scholar 

  50. Joshi S, Singh-Moon R, Wang M, Bigio IJ (2014) Transient cerebral hypoperfusion assisted intra- arterial delivery of mitoxantrone in C6 glioma bearing rats. J Neurosurg Anesthesiol 26(4):482

    Google Scholar 

  51. Gelman M, Chakeres DW, Newton HB (1999) Brain tumors: complications of cerebral angiography accompanied by intraarterial chemotherapy. Radiology 213(1):135–140

    Article  CAS  PubMed  Google Scholar 

  52. Koganemaru M, Abe T, Anai H, Tanaka N, Nonoshita M, Iwamoto R, Kusumoto M, Kuhara A, Kugiyama T, Hayabuchi N (2012) A newly developed double lumen microballoon catheter with a side hole: initial experience of intraarterial infusion chemotherapy and/or embolization. Jpn J Radiol 30(10):870–874. doi:10.1007/s11604-012-0128-x

    Article  PubMed  Google Scholar 

  53. Claus EB, Walsh KM, Wiencke JK, Molinaro AM, Wiemels JL, Schildkraut JM, Bondy ML, Berger M, Jenkins R, Wrensch M (2015) Survival and low-grade glioma: the emergence of genetic information. Neurosurg Focus 38(1):E6. doi:10.3171/2014.10.FOCUS12367

    Article  PubMed  PubMed Central  Google Scholar 

  54. Iaccarino C, Orlandi E, Ruggeri F, Nicoli D, Torricelli F, Maggi M, Cerasti D, Pisanello A, Pedrazzi G, Froio E, Crafa P, D’Abbiero N, Michiara M, Ghadirpour R, Servadei F (2015) Prognostic value of MGMT promoter status in non-resectable glioblastoma after adjuvant therapy. Clin Neurol Neurosurg 132C:1–8. doi:10.1016/j.clineuro.2015.01.029

    Article  Google Scholar 

  55. Pile-Spellman J, Young WL, Joshi S, Duong DH, Vang MC, Hartmann A, Kahn RA, Rubin DA, Prestigiacomo CJ, Ostapkovich ND (1999) Adenosine-induced cardiac pause for endovascular embolization of cerebral arteriovenous malformations: technical case report. Neurosurgery 44(4):881 discussion 886–887

    Article  CAS  PubMed  Google Scholar 

  56. Newton HB (2006) Advances in strategies to improve drug delivery to brain tumors. Expert Rev Neurotherapeutics 6(10):1495–1509. doi:10.1586/14737175.6.10.1495

    Article  CAS  Google Scholar 

  57. Greig NH, Daly EM, Sweeney DJ, Rapoport SI (1990) Pharmacokinetics of chlorambucil-tertiary butyl ester, a lipophilic chlorambucil derivative that achieves and maintains high concentrations in brain. Cancer Chemothe Pharmacol 25(5):320–325

    Article  CAS  Google Scholar 

  58. Friden PM, Walus LR, Musso GF, Taylor MA, Malfroy B, Starzyk RM (1991) Anti-transferrin receptor antibody and antibody-drug conjugates cross the blood-brain barrier. Proc Natl Acad Sci U S A 88(11):4771–4775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Shi NQ, Gao W, Xiang B, Qi XR (2012) Enhancing cellular uptake of activable cell-penetrating peptide-doxorubicin conjugate by enzymatic cleavage. Intern J Nanomed 7:1613–1621. doi:10.2147/IJN.S30104

    CAS  Google Scholar 

  60. Joshi S, Singh-Moon R, Wang M, Chaudhuri DB, Ellis JA, Bruce JN, Bigio IJ, Straubinger RM (2014) Cationic surface charge enhances early regional deposition of liposomes after intracarotid injection. J Neurooncol. doi:10.1007/s11060-014-1584-1

    Google Scholar 

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National Cancer Institute at the National Institutes of Health RO1-CA-138643.

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Joshi, S., Ellis, J.A., Ornstein, E. et al. Intraarterial drug delivery for glioblastoma mutiforme. J Neurooncol 124, 333–343 (2015). https://doi.org/10.1007/s11060-015-1846-6

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