Irinotecan in Combination With Cisplatin in Pediatric Patients With Unfavorable Prognosis Gliomas

Summary

Tumours of the brain and of the central nervous system (CNS) are the most common solid tumours in children. Amongst these, gliomas are the most frequent, although this term covers different histological subtypes, the most frequent being astrocytoma. However, they are rare diseases of low prevalence. The interest in the cisplatin/irinotecan combination in brain tumours motivated a previous pilot study at our hospital, with encouraging results. This experience, together with the need for new strategies for high-risk pediatric gliomas has motivated the conduct of this study.

Timeline

Start

2009-11

Primary completion

2014-06

Completion

2015-03

Publications

• Background Alonso M, Hamelin R, Kim M, Porwancher K, Sung T, Parhar P, Miller DC, Newcomb EW. Microsatellite instability occurs in distinct subtypes of pediatric but not adult central nervous system tumors. Cancer Res. 2001 Mar 1;61(5):2124-8.
• Background Blaney S, Berg SL, Pratt C, Weitman S, Sullivan J, Luchtman-Jones L, Bernstein M. A phase I study of irinotecan in pediatric patients: a pediatric oncology group study. Clin Cancer Res. 2001 Jan;7(1):32-7.
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• Background Bomgaars L, Kerr J, Berg S, Kuttesch J, Klenke R, Blaney SM. A phase I study of irinotecan administered on a weekly schedule in pediatric patients. Pediatr Blood Cancer. 2006 Jan;46(1):50-5. doi: 10.1002/pbc.20355.
• Background Bomgaars LR, Bernstein M, Krailo M, Kadota R, Das S, Chen Z, Adamson PC, Blaney SM. Phase II trial of irinotecan in children with refractory solid tumors: a Children's Oncology Group Study. J Clin Oncol. 2007 Oct 10;25(29):4622-7. doi: 10.1200/JCO.2007.11.6103.
• Background Bouffet E, Mottolese C, Jouvet A, Philip I, Frappaz D, Carrie C, Brunat-Mentigny M. Etoposide and thiotepa followed by ABMT (autologous bone marrow transplantation) in children and young adults with high-grade gliomas. Eur J Cancer. 1997 Jan;33(1):91-5. doi: 10.1016/s0959-8049(96)00369-3.
• Background Brat DJ, Shehata BM, Castellano-Sanchez AA, Hawkins C, Yost RB, Greco C, Mazewski C, Janss A, Ohgaki H, Perry A. Congenital glioblastoma: a clinicopathologic and genetic analysis. Brain Pathol. 2007 Jul;17(3):276-81. doi: 10.1111/j.1750-3639.2007.00071.x. Epub 2007 Apr 23.
• Background Broniscer A, Chintagumpala M, Fouladi M, Krasin MJ, Kocak M, Bowers DC, Iacono LC, Merchant TE, Stewart CF, Houghton PJ, Kun LE, Ledet D, Gajjar A. Temozolomide after radiotherapy for newly diagnosed high-grade glioma and unfavorable low-grade glioma in children. J Neurooncol. 2006 Feb;76(3):313-9. doi: 10.1007/s11060-005-7409-5.
• Background Coggins CA, Elion GB, Houghton PJ, Hare CB, Keir S, Colvin OM, Bigner DD, Friedman HS. Enhancement of irinotecan (CPT-11) activity against central nervous system tumor xenografts by alkylating agents. Cancer Chemother Pharmacol. 1998;41(6):485-90. doi: 10.1007/s002800050771.
• Background Cosetti M, Wexler LH, Calleja E, Trippett T, LaQuaglia M, Huvos AG, Gerald W, Healey JH, Meyers PA, Gorlick R. Irinotecan for pediatric solid tumors: the Memorial Sloan-Kettering experience. J Pediatr Hematol Oncol. 2002 Feb;24(2):101-5. doi: 10.1097/00043426-200202000-00009.
• Background Crews KR, Stewart CF, Jones-Wallace D, Thompson SJ, Houghton PJ, Heideman RL, Fouladi M, Bowers DC, Chintagumpala MM, Gajjar A. Altered irinotecan pharmacokinetics in pediatric high-grade glioma patients receiving enzyme-inducing anticonvulsant therapy. Clin Cancer Res. 2002 Jul;8(7):2202-9.
• Background Donson AM, Addo-Yobo SO, Handler MH, Gore L, Foreman NK. MGMT promoter methylation correlates with survival benefit and sensitivity to temozolomide in pediatric glioblastoma. Pediatr Blood Cancer. 2007 Apr;48(4):403-7. doi: 10.1002/pbc.20803.
• Background Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, Baylin SB, Herman JG. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med. 2000 Nov 9;343(19):1350-4. doi: 10.1056/NEJM200011093431901.
• Background Fallik D, Borrini F, Boige V, Viguier J, Jacob S, Miquel C, Sabourin JC, Ducreux M, Praz F. Microsatellite instability is a predictive factor of the tumor response to irinotecan in patients with advanced colorectal cancer. Cancer Res. 2003 Sep 15;63(18):5738-44.
• Background Finlay JL, Geyer JR, Turski PA, Yates AJ, Boyett JM, Allen JC, Packer RJ. Pre-irradiation chemotherapy in children with high-grade astrocytoma: tumor response to two cycles of the '8-drugs-in-1-day' regimen. A Childrens Cancer Group study, CCG-945. J Neurooncol. 1994;21(3):255-65. doi: 10.1007/BF01063775.
• Background Furman WL, Stewart CF, Poquette CA, Pratt CB, Santana VM, Zamboni WC, Bowman LC, Ma MK, Hoffer FA, Meyer WH, Pappo AS, Walter AW, Houghton PJ. Direct translation of a protracted irinotecan schedule from a xenograft model to a phase I trial in children. J Clin Oncol. 1999 Jun;17(6):1815-24. doi: 10.1200/JCO.1999.17.6.1815.
• Background Gallia GL, Rand V, Siu IM, Eberhart CG, James CD, Marie SK, Oba-Shinjo SM, Carlotti CG, Caballero OL, Simpson AJ, Brock MV, Massion PP, Carson BS Sr, Riggins GJ. PIK3CA gene mutations in pediatric and adult glioblastoma multiforme. Mol Cancer Res. 2006 Oct;4(10):709-14. doi: 10.1158/1541-7786.MCR-06-0172.
• Background Gilbertson RJ, Hill DA, Hernan R, Kocak M, Geyer R, Olson J, Gajjar A, Rush L, Hamilton RL, Finkelstein SD, Pollack IF. ERBB1 is amplified and overexpressed in high-grade diffusely infiltrative pediatric brain stem glioma. Clin Cancer Res. 2003 Sep 1;9(10 Pt 1):3620-4.
• Background Gnekow AK, Kortmann RD, Pietsch T, Emser A. Low grade chiasmatic-hypothalamic glioma-carboplatin and vincristin chemotherapy effectively defers radiotherapy within a comprehensive treatment strategy -- report from the multicenter treatment study for children and adolescents with a low grade glioma -- HIT-LGG 1996 -- of the Society of Pediatric Oncology and Hematology (GPOH). Klin Padiatr. 2004 Nov-Dec;216(6):331-42. doi: 10.1055/s-2004-832355.
• Background Grill J, Couanet D, Cappelli C, Habrand JL, Rodriguez D, Sainte-Rose C, Kalifa C. Radiation-induced cerebral vasculopathy in children with neurofibromatosis and optic pathway glioma. Ann Neurol. 1999 Mar;45(3):393-6. doi: 10.1002/1531-8249(199903)45:33.0.co;2-b.
• Background Grovas AC, Boyett JM, Lindsley K, Rosenblum M, Yates AJ, Finlay JL. Regimen-related toxicity of myeloablative chemotherapy with BCNU, thiotepa, and etoposide followed by autologous stem cell rescue for children with newly diagnosed glioblastoma multiforme: report from the Children's Cancer Group. Med Pediatr Oncol. 1999 Aug;33(2):83-7. doi: 10.1002/(sici)1096-911x(199908)33:23.0.co;2-g.
• Background Hegi ME, Diserens AC, Godard S, Dietrich PY, Regli L, Ostermann S, Otten P, Van Melle G, de Tribolet N, Stupp R. Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide. Clin Cancer Res. 2004 Mar 15;10(6):1871-4. doi: 10.1158/1078-0432.ccr-03-0384.
• Background Hertzberg RP, Caranfa MJ, Holden KG, Jakas DR, Gallagher G, Mattern MR, Mong SM, Bartus JO, Johnson RK, Kingsbury WD. Modification of the hydroxy lactone ring of camptothecin: inhibition of mammalian topoisomerase I and biological activity. J Med Chem. 1989 Mar;32(3):715-20. doi: 10.1021/jm00123a038.

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Indications