Prevention of Thrombocytopenia in Glioblastoma Patients

Summary

Chemotherapy used in the treatment of primitive tumors of the central nervous system has a particularly important platelet toxicity compared to chemotherapy used for treatment of other tumors. Chemotherapy postponed for toxicity is often due to thrombocytopenia (TP). The TP and/or the other anomalies of coagulation, which can be spontaneous (Rogers, 2004) or induced (Gerber, 2006) can have dramatic consequences: * specifically neurological (intratumoral bleeding with particularly important neovascularization) with a functional aggravation and sometimes involvement of vital prognosis, * digestive (Garcia-Rodiguez, 2001) in patients receiving long term treatment with corticoids (potential gastric toxicity). The encouraging results from the EORTC/NCIC trial by Stupp (median survival among patients with newly diagnosed glioblastoma is 14.6 months with an estimated 5-year survival of 9, 8%), has changed the standard of care of these patients (Stupp et al., 2009). Patients with newly diagnosed, histologically confirmed glioblastoma receive radiotherapy (2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) plus continuous daily Temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant Temozolomide (TMZ) (150 to 200 mg per square meter for 5 days during each 28-day cycle). The Stupp regimen is currently the treatment of reference for glioblastoma and is used as a basis in various clinical studies with new agents. This study aims to evaluate Romiplostim for the treatment of TP secondary to initial TMZ chemotherapy of glioblastomas.

Timeline

Start

2014-07-10

Primary completion

2017-12-14

Completion

2017-12-14

Publications

• Background Armstrong TS, Cao Y, Scheurer ME, Vera-Bolanos E, Manning R, Okcu MF, Bondy M, Zhou R, Gilbert MR. Risk analysis of severe myelotoxicity with temozolomide: the effects of clinical and genetic factors. Neuro Oncol. 2009 Dec;11(6):825-32. doi: 10.1215/15228517-2008-120.
• Background Gerber DE, Grossman SA, Zeltzman M, Parisi MA, Kleinberg L. The impact of thrombocytopenia from temozolomide and radiation in newly diagnosed adults with high-grade gliomas. Neuro Oncol. 2007 Jan;9(1):47-52. doi: 10.1215/15228517-2006-024. Epub 2006 Nov 15.
• Background George JN, Raskob GE, Shah SR, Rizvi MA, Hamilton SA, Osborne S, Vondracek T. Drug-induced thrombocytopenia: a systematic review of published case reports. Ann Intern Med. 1998 Dec 1;129(11):886-90. doi: 10.7326/0003-4819-129-11_part_1-199812010-00009.
• Background Kuter DJ, Rummel M, Boccia R, Macik BG, Pabinger I, Selleslag D, Rodeghiero F, Chong BH, Wang X, Berger DP. Romiplostim or standard of care in patients with immune thrombocytopenia. N Engl J Med. 2010 Nov 11;363(20):1889-99. doi: 10.1056/NEJMoa1002625.
• Background Molineux G. The development of romiplostim for patients with immune thrombocytopenia. Ann N Y Acad Sci. 2011 Mar;1222:55-63. doi: 10.1111/j.1749-6632.2011.05975.x.
• Background Sure D, Dunn I, Norden A, Anderson WS. Intracerebral hemorrhage secondary to thrombocytopenia in a patient treated with temozolomide. Clin Neurol Neurosurg. 2010 Oct;112(8):741-2. doi: 10.1016/j.clineuro.2010.04.005.
• Background Mutter N, Stupp R. Temozolomide: a milestone in neuro-oncology and beyond? Expert Rev Anticancer Ther. 2006 Aug;6(8):1187-204. doi: 10.1586/14737140.6.8.1187.
• Background Oh J, Kutas GJ, Davey P, Morrison M, Perry JR. Aplastic anemia with concurrent temozolomide treatment in a patient with glioblastoma multiforme. Curr Oncol. 2010 Aug;17(4):124-6. doi: 10.3747/co.v17i4.526.
• Le Rhun E, Devos P, Houillier C, Cartalat S, Chinot O, Di Stefano AL, Lepage C, Reyns N, Dubois F, Weller M. Romiplostim for temozolomide-induced thrombocytopenia in glioblastoma: The PLATUM trial. Neurology. 2019 Nov 5;93(19):e1799-e1806. doi: 10.1212/WNL.0000000000008440. Epub 2019 Oct 4.

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