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Intra-arterial carboplatin as a salvage strategy in the treatment of recurrent glioblastoma multiforme

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Abstract

The first-line treatment of glioblastoma typically consists of a maximal surgical resection, followed by a combination of radio-chemotherapy with temozolomide. There is however no consensus regarding optimal therapeutic approaches at relapse. The following phase II study explored the therapeutic gain obtained when exposing these patients to a combination of intra-arterially administered carboplatin and melphalan at first or second relapse as a salvage treatment in recurrent glioblastoma. Fifty-one consecutive patients diagnosed with glioblastoma were accrued and offered this treatment at first or second relapse. A Karnofsky score of ≥60 was required, and when appropriate, patients were first reoperated prior to accrual. Patients enrolled were treated every 4 weeks (1 cycle) for up to 12 cycles. Progression was evaluated by Macdonald criteria. Primary end point surrogates were overall survival from diagnosis and study entry. Median survival from diagnosis and study entry was 23 and 11 months, respectively. The median time to progression was 5.2 months. All patients enrolled were treated for a minimum of 2 cycles. Hematologic toxicity was manageable, with an 8 % of grade II neutropenia, 12 % of grade II thrombocytopenia and 7 % of grade III thrombocytopenia. This therapeutic strategy represents an adequate option in the second-line treatment of recurrent glioblastoma. The adjunction of an osmotic permeabilization could be considered to further expand delivery, and hopefully improve survival in these patients.

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References

  1. Stupp R, Dietrich P, Kraljevic S et al (2002) Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol 20(5):1375

    Article  CAS  PubMed  Google Scholar 

  2. Stupp R, Mason W, van den Bent M et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987

    Article  CAS  PubMed  Google Scholar 

  3. Perry JR, Rizek P, Cashman R, Morrison M, Morrison T (2008) Temozolomide rechallenge in recurrent malignant glioma by using a continuous temozolomide schedule: the “rescue” approach. Cancer 113(8):2152–2157. doi:10.1002/cncr.23813

    Article  CAS  PubMed  Google Scholar 

  4. Butowski NA, Sneed P, Chang SM (2006) Diagnosis and treatment of recurrent high-grade astrocytoma. J Clin Oncol 24:1273–1280

    Article  CAS  PubMed  Google Scholar 

  5. Carrillo JA, Munoz CA (2012) Alternative chemotherapeutic agents: nitrosoureas, cisplatin, irinotecan. Neurosurg Clin N Am 23(2):297–306. doi:10.1016/j.nec.2012.01.005

    Article  PubMed  Google Scholar 

  6. Morris PG (2012) Bevacizumab is an active agent for recurrent high-grade glioma, but do we need randomized controlled trials? Anticancer Drugs. doi:10.1097/CAD.0b013e3283528847

    Google Scholar 

  7. Reardon DA, Herndon JE, Peters K et al (2012) Outcome after bevacizumab clinical trial therapy among recurrent grade III malignant glioma patients. J Neurooncol 107(1):213–221. doi:10.1007/s11060-011-0740-0

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Narayana A, Kunnakkat SD, Medabalmi P et al (2012) Change in pattern of relapse after antiangiogenic therapy in high-grade glioma. Int J Radiat Oncol Biol Phys 82(1):77–82. doi:10.1016/j.ijrobp.2010.10.038

    Article  PubMed  Google Scholar 

  9. Pitz MW, Desai A, Grossman SA, Blakeley JO (2011) Tissue concentration of systemically administered antineoplastic agents in human brain tumors. J Neurooncol. doi:10.1007/s11060-011-0564-y

    PubMed Central  PubMed  Google Scholar 

  10. Reichel A (2009) Addressing central nervous system (CNS) penetration in drug discovery: basics and implications of the evolving new concept. Chem Biodivers 6(11):2030–2049. doi:10.1002/cbdv.200900103

    Article  CAS  PubMed  Google Scholar 

  11. Abbott NJ, Ronnback L, Hansson E (2006) Astrocyte–endothelial interactions at the blood–brain barrier. Nat Rev Neurosci 7(1):41–53

    Article  CAS  PubMed  Google Scholar 

  12. Deeken JF, Loscher W (2007) The blood–brain barrier and cancer: transporters, treatment, and Trojan horses. Clin Cancer Res 13(6):1663–1674

    Article  CAS  PubMed  Google Scholar 

  13. Pardridge WM (2007) Blood–brain barrier delivery. Drug Discov Today 12(1–2):54–61

    Article  CAS  PubMed  Google Scholar 

  14. Kroll RA, Neuwelt EA (1998) Outwitting the blood-brain barrier for therapeutic purposes: osmotic opening and other means. Neurosurgery 42(5):1083–1099 discussion 1099–1100

    Article  CAS  PubMed  Google Scholar 

  15. Rapoport SI, Hori M, Klatzo I (1972) Testing of a hypothesis for osmotic opening of the blood–brain barrier. Am J Physiol 223(2):323–331

    CAS  PubMed  Google Scholar 

  16. Bellavance MA, Blanchette M, Fortin D (2008) Recent advances in blood–brain barrier disruption as a CNS delivery strategy. AAPS J 10(1):166–177

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Tosoni A, Ermani M, Brandes AA (2004) The pathogenesis and treatment of brain metastases: a comprehensive review. Crit Rev Oncol Hematol 52:199–215

    Article  PubMed  Google Scholar 

  18. Sato S, Kawase T, Harada S, Takayama H, Suga S (1998) Effect of hyperosmotic solutions on human brain tumour vasculature. Acta Neurochir (Wien) 140(11):1135–1141 discussion 1141–1142

    Article  CAS  Google Scholar 

  19. 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. Cancer 103(12):2606–2615

    Article  PubMed  Google Scholar 

  20. Fortin D, Gendron C, Boudrias M, Garant MP (2007) Enhanced chemotherapy delivery by intraarterial infusion and blood–brain barrier disruption in the treatment of cerebral metastasis. Cancer 109(4):751–760

    Article  CAS  PubMed  Google Scholar 

  21. Newton HB, Slivka MA, Volpi C et al (2003) Intra-arterial carboplatin and intravenous etoposide for the treatment of metastatic brain tumors. J Neurooncol 61:35–44

    Article  PubMed  Google Scholar 

  22. Kurpad SN, Friedman HS, Archer GE, McLendon RE, Petros WM, Fuchs HE et al (1995) Intraarterial administration of melphalan for treatment of intracranial human glioma xenografts in athymic rats. Cancer Res 55(17):3803–3809

    CAS  PubMed  Google Scholar 

  23. Quant EC, Wen PY (2011) Response assessment in neuro-oncology. Curr Oncol Rep 13(1):50–56. doi:10.1007/s11912-010-0143-y

    Article  PubMed  Google Scholar 

  24. Fortin D (2012) The blood–brain barrier: its influence in the treatment of brain tumors metastases. Curr Cancer Drug Targets 12(3):247–259

    Article  CAS  PubMed  Google Scholar 

  25. Calatozzolo C, Gelati M, Ciusani E et al (2005) Expression of drug resistance proteins Pgp, MRP1, MRP3, MRP5 and GST-pi in human glioma. J Neurooncol 74(2):113–121. doi:10.1007/s11060-004-6152-7

    Article  CAS  PubMed  Google Scholar 

  26. Boulikas T (2007) Molecular mechanisms of cisplatin and its liposomally encapsulated form, LipoplatinTM. LipoplatinTM as a chemotherapy and antiangiogenesis drug. Cancer Ther 5:349–376

    Google Scholar 

  27. Zustovich F, Lombardi G, Della Puppa A, Rotilio A, Scienza R, Pastorelli D (2009) A phase II study of cisplatin and temozolomide in heavily pre-treated patients with temozolomide-refractory high-grade malignant glioma. Anticancer Res 29(10):4275–4279

    CAS  PubMed  Google Scholar 

  28. Zustovich F, Cartei G, Ceravolo R et al (2007) A phase I study of cisplatin, temozolomide and thalidomide in patients with malignant brain tumors. Anticancer Res 27(2):1019–1024

    CAS  PubMed  Google Scholar 

  29. Frenay M, Lebrun C, Lonjon M, Bondiau PY, Chatel M (2000) Up-front chemotherapy with fotemustine (F)/cisplatin (CDDP)/etoposide (VP16) regimen in the treatment of 33 non-removable glioblastomas. Eur J Cancer 36(8):1026–1031

    Article  CAS  PubMed  Google Scholar 

  30. Brambilla Bas M, Boccardo M (1993) Intracarotid cisplatin chemotherapy for high-grade astrocytomas. J Neurosurg Sci 37(2):83–86

    CAS  PubMed  Google Scholar 

  31. Tfayli A, Hentschel P, Madajewicz S et al (1999) Toxicities related to intraarterial infusion of cisplatin and etoposide in patients with brain tumors. J Neurooncol 42(1):73–77

    Article  CAS  PubMed  Google Scholar 

  32. Madajewicz S, Chowhan N, Tfayli A et al (2000) Therapy for patients with high grade astrocytoma using intraarterial chemotherapy and radiation therapy. Cancer 88(10):2350–2356

    Article  CAS  PubMed  Google Scholar 

  33. Wu HM, Lee AG, Lehane DE, Chi TL, Lewis RA (1997) Ocular and orbital complications of intraarterial cisplatin: a case report. J Neuroophthalmol 17(3):195–198

    Article  CAS  PubMed  Google Scholar 

  34. Schäfer N, Tichy J, Thanendrarajan S et al (2011) Ifosfamide, carboplatin and etoposide in recurrent malignant glioma. Oncology 80(5–6):330–332. doi:10.1159/000330358

    Article  PubMed  Google Scholar 

  35. Tang P, Roldan G, Brasher PMA et al (2006) A phase II study of carboplatin and chronic high-dose tamoxifen in patients with recurrent malignant glioma. J Neurooncol 78(3):311–316. doi:10.1007/s11060-005-9104-y

    Article  CAS  PubMed  Google Scholar 

  36. Francesconi AB, Dupre S, Matos M et al (2010) Carboplatin and etoposide combined with bevacizumab for the treatment of recurrent glioblastoma multiforme. J Clin Neurosci 17(8):970–974. doi:10.1016/j.jocn.2009.12.009

    Article  CAS  PubMed  Google Scholar 

  37. Doolittle ND, Miner ME, Hall WA et al (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 

  38. Mathieu D, Lecomte R, Tsanaclis AM, Larouche A, Fortin D (2007) Standardization and detailed characterization of the syngeneic Fischer/F98 glioma model. Can J Neurol Sci 34(3):296–306

    PubMed  Google Scholar 

  39. Charest G, Sanche L, Fortin D, Mathieu D, Paquette B (2012) Glioblastoma treatment: bypassing the toxicity of platinum compounds by using liposomal formulation and increasing treatment efficiency with concomitant radiotherapy. Int J Radiat Oncol Biol Phys. doi:10.1016/j.ijrobp.2011.10.054

    PubMed Central  PubMed  Google Scholar 

  40. Kleinschmidt-DeMasters BK, Geier JM (1989) Pathology of high-dose intraarterial BCNU. Surg Neurol 31(6):435–443

    Article  CAS  PubMed  Google Scholar 

  41. Tonn JC, Roosen K, Schachenmayr W (1991) Brain necroses after intraarterial chemotherapy and irradiation of malignant gliomas: a complication of both ACNU and BCNU? J Neurooncol 11(3):241–242

    Article  CAS  PubMed  Google Scholar 

  42. Jiglaire CJ, Baeza-Kallee N, Denicolaï E, Barets D, Metellus P, Padovani L et al (2013) Cultures of glioblastoma in three-dimensional hydrogel maintain the original tumor growth behavior and are suitable for preclinical drug and radiation sensitivity screening. Exp Cell Res 12:1–10

    Google Scholar 

  43. Gwak H-S, Park HJ, Yoo H, Youn SM, Rhee CH, Lee SH (2011) Chemotherapy for malignant gliomas based on histoculture drug response assay: a pilot study. J Korean Neurosurg Soc 50(5):426

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Iwadate Y, Fujimoto S, Namba H, Yamaura A (2003) Promising survival for patients with glioblastoma multiforme treated with individualised chemotherapy based on in vitro drug sensitivity testing. Br J Cancer 89(10):1896–1900

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Bank research chair on brain tumors, held by D. Fortin. The protocol was approved by the institutional review board, and informed consent was obtained for each patient in accordance to institutional regulation prior to accrual.

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The authors have no financial disclosure and there is no conflict of interest to declare.

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Correspondence to David Fortin.

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

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  • DOI: https://doi.org/10.1007/s11060-014-1504-4

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