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Published in: Child's Nervous System 9/2011

01-09-2011 | Original Paper

Combination chemotherapy with ifosfamide, cisplatin, and etoposide for medulloblastoma: single-institute experience and differences in efficacy for subgroups of medulloblastoma

Authors: Ryuta Saito, Toshihiro Kumabe, Yukihiko Sonoda, Masayuki Kanamori, Yoji Yamashita, Mika Watanabe, Teiji Tominaga

Published in: Child's Nervous System | Issue 9/2011

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Abstract

Purpose

Treatment for medulloblastoma consists of surgical resection, radiation therapy, and chemotherapy. In Japan, ICE chemotherapy consisting of cisplatin, ifosfamide, and etoposide is one of the most common regimens. Here, we summarize the toxicity and efficacy of ICE chemotherapy and evaluate the usefulness of the recently introduced molecular classification scheme to predict the outcome.

Methods

Seventeen patients with medulloblastoma treated by ICE chemotherapy as an initial therapy at our institute were retrospectively reviewed. Eleven were categorized in the standard-risk group and six in the high-risk group. All patients underwent maximum cytoreductive surgery, radiation therapy, and ICE chemotherapy. Operative specimens were subjected to immunohistochemical staining using four antibodies—DKK1, SFRP1, NPR3, and KCNA1—to classify the cases into four subgroups, WNT group, SHH group, group C, and group D, respectively.

Results

ICE chemotherapy following surgery and radiation therapy was tolerable in most patients with appropriate management, although myelosuppression and hearing disturbance occurred. There was no significant difference in survival between patients with standard-risk disease and high-risk disease. Five-year survival and 5-year progression-free survival for the 17 patients were 80.7% and 63.5%, respectively. Three patients were classified as WNT group, 2 as SHH group, 1 as group C, and 11 as group D. Group D tended to have poorer prognosis after ICE chemotherapy.

Conclusions

ICE chemotherapy was tolerable and active against medulloblastomas. Patients categorized as group D tended to have worse outcome after ICE chemotherapy.
Literature
1.
go back to reference Crawford JR, MacDonald TJ, Packer RJ (2007) Medulloblastoma in childhood: new biological advances. Lancet Neurol 6:1073–1085PubMedCrossRef Crawford JR, MacDonald TJ, Packer RJ (2007) Medulloblastoma in childhood: new biological advances. Lancet Neurol 6:1073–1085PubMedCrossRef
2.
go back to reference Deutsch M, Thomas PR, Krischer J, Boyett JM, Albright L, Aronin P, Langston J, Allen JC, Packer RJ, Linggood R, Mulhern R, Stanley P, Stehbens JA, Duffner P, Kun L, Rorke L, Cherlow J, Freidman H, Finlay JL, Vietti T (1996) Results of a prospective randomized trial comparing standard dose neuraxis irradiation (3,600 cGy/20) with reduced neuraxis irradiation (2,340 cGy/13) in patients with low-stage medulloblastoma. A combined Children's Cancer Group–Pediatric Oncology Group Study. Pediatr Neurosurg 24:167–176PubMedCrossRef Deutsch M, Thomas PR, Krischer J, Boyett JM, Albright L, Aronin P, Langston J, Allen JC, Packer RJ, Linggood R, Mulhern R, Stanley P, Stehbens JA, Duffner P, Kun L, Rorke L, Cherlow J, Freidman H, Finlay JL, Vietti T (1996) Results of a prospective randomized trial comparing standard dose neuraxis irradiation (3,600 cGy/20) with reduced neuraxis irradiation (2,340 cGy/13) in patients with low-stage medulloblastoma. A combined Children's Cancer Group–Pediatric Oncology Group Study. Pediatr Neurosurg 24:167–176PubMedCrossRef
3.
go back to reference Giangaspero F, Eberhart CG, Haapasalo H, Pietsch T, Wiestler OD, Ellison DW (2007) Medulloblastoma. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO classification of tumours of the central nervous system. IARC, Lyon, pp 132–140 Giangaspero F, Eberhart CG, Haapasalo H, Pietsch T, Wiestler OD, Ellison DW (2007) Medulloblastoma. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO classification of tumours of the central nervous system. IARC, Lyon, pp 132–140
4.
go back to reference Jakacki RI (2005) Treatment strategies for high-risk medulloblastoma and supratentorial primitive neuroectodermal tumors. Review of the literature. J Neurosurg 102(1 Suppl):44–52PubMed Jakacki RI (2005) Treatment strategies for high-risk medulloblastoma and supratentorial primitive neuroectodermal tumors. Review of the literature. J Neurosurg 102(1 Suppl):44–52PubMed
5.
go back to reference Kochi M, Kuratsu J, Mihara Y, Takaki S, Seto H, Uemura S, Ushio Y (1993) Ventriculolumbar perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride. Neurosurgery 33:817–823PubMedCrossRef Kochi M, Kuratsu J, Mihara Y, Takaki S, Seto H, Uemura S, Ushio Y (1993) Ventriculolumbar perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride. Neurosurgery 33:817–823PubMedCrossRef
6.
go back to reference Kortmann RD, Kühl J, Timmermann B, Mittler U, Urban C, Budach V, Richter E, Willich N, Flentje M, Berthold F, Slavc I, Wolff J, Meisner C, Wiestler O, Sörensen N, Warmuth-Metz M, Bamberg M (2000) Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: results of the German prospective randomized trial HIT '91. Int J Radiat Oncol Biol Phys 46:269–279PubMedCrossRef Kortmann RD, Kühl J, Timmermann B, Mittler U, Urban C, Budach V, Richter E, Willich N, Flentje M, Berthold F, Slavc I, Wolff J, Meisner C, Wiestler O, Sörensen N, Warmuth-Metz M, Bamberg M (2000) Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: results of the German prospective randomized trial HIT '91. Int J Radiat Oncol Biol Phys 46:269–279PubMedCrossRef
7.
go back to reference Northcott PA, Korshunov A, Witt H, Hielscher T, Eberhart C, Mack S, Bouffet E, Clifford SC, Hawkins C, French P, Rutka JT, Pfister S, Taylor MD (2011) Medulloblastoma comprises four distinct molecular variants. J Clin Oncol 29(11):1408–1414PubMedCrossRef Northcott PA, Korshunov A, Witt H, Hielscher T, Eberhart C, Mack S, Bouffet E, Clifford SC, Hawkins C, French P, Rutka JT, Pfister S, Taylor MD (2011) Medulloblastoma comprises four distinct molecular variants. J Clin Oncol 29(11):1408–1414PubMedCrossRef
8.
go back to reference Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC, Robertson PL, Bayer L, LaFond D, Donahue BR, Marymont MH, Muraszko K, Langston J, Sposto R (2006) Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol 24:4202–4208PubMedCrossRef Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC, Robertson PL, Bayer L, LaFond D, Donahue BR, Marymont MH, Muraszko K, Langston J, Sposto R (2006) Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol 24:4202–4208PubMedCrossRef
9.
go back to reference Packer RJ, Goldwein J, Nicholson HS, Vezina LG, Allen JC, Ris MD, Muraszko K, Rorke LB, Wara WM, Cohen BH, Boyett JM (1999) Treatment of children with medulloblastomas with reduced-dose craniospinal radiation therapy and adjuvant chemotherapy: a Children's Cancer Group Study. J Clin Oncol 17:2127–2136PubMed Packer RJ, Goldwein J, Nicholson HS, Vezina LG, Allen JC, Ris MD, Muraszko K, Rorke LB, Wara WM, Cohen BH, Boyett JM (1999) Treatment of children with medulloblastomas with reduced-dose craniospinal radiation therapy and adjuvant chemotherapy: a Children's Cancer Group Study. J Clin Oncol 17:2127–2136PubMed
10.
go back to reference Packer RJ, Sutton LN, Goldwein JW, Perilongo G, Bunin G, Ryan J, Cohen BH, D'Angio G, Kramer ED, Zimmerman RA, Rorke LB, Evans AE, Schut L (1991) Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma. J Neurosurg 74:433–440PubMedCrossRef Packer RJ, Sutton LN, Goldwein JW, Perilongo G, Bunin G, Ryan J, Cohen BH, D'Angio G, Kramer ED, Zimmerman RA, Rorke LB, Evans AE, Schut L (1991) Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma. J Neurosurg 74:433–440PubMedCrossRef
11.
go back to reference Packer RJ, Vezina G (2008) Management of and prognosis with medulloblastoma: therapy at a crossroads. Arch Neurol 65:1419–1424PubMedCrossRef Packer RJ, Vezina G (2008) Management of and prognosis with medulloblastoma: therapy at a crossroads. Arch Neurol 65:1419–1424PubMedCrossRef
12.
go back to reference Sawamura Y, Ikeda J, Ishii N, Kato T, Tada M, Abe H, Shirato H (1996) Combined irradiation and chemotherapy using ifosfamide, cisplatin, and etoposide for children with medulloblastoma/posterior fossa primitive neuroectodermal tumor—results of a pilot study. Neurol Med Chir Tokyo 36:632–638PubMedCrossRef Sawamura Y, Ikeda J, Ishii N, Kato T, Tada M, Abe H, Shirato H (1996) Combined irradiation and chemotherapy using ifosfamide, cisplatin, and etoposide for children with medulloblastoma/posterior fossa primitive neuroectodermal tumor—results of a pilot study. Neurol Med Chir Tokyo 36:632–638PubMedCrossRef
13.
go back to reference Thomas PR, Deutsch M, Kepner JL, Boyett JM, Krischer J, Aronin P, Albright L, Allen JC, Packer RJ, Linggood R, Mulhern R, Stehbens JA, Langston J, Stanley P, Duffner P, Rorke L, Cherlow J, Friedman HS, Finlay JL, Vietti TJ, Kun LE (2000) Low-stage medulloblastoma: final analysis of trial comparing standard-dose with reduced-dose neuraxis irradiation. J Clin Oncol 18:3004–3011PubMed Thomas PR, Deutsch M, Kepner JL, Boyett JM, Krischer J, Aronin P, Albright L, Allen JC, Packer RJ, Linggood R, Mulhern R, Stehbens JA, Langston J, Stanley P, Duffner P, Rorke L, Cherlow J, Friedman HS, Finlay JL, Vietti TJ, Kun LE (2000) Low-stage medulloblastoma: final analysis of trial comparing standard-dose with reduced-dose neuraxis irradiation. J Clin Oncol 18:3004–3011PubMed
Metadata
Title
Combination chemotherapy with ifosfamide, cisplatin, and etoposide for medulloblastoma: single-institute experience and differences in efficacy for subgroups of medulloblastoma
Authors
Ryuta Saito
Toshihiro Kumabe
Yukihiko Sonoda
Masayuki Kanamori
Yoji Yamashita
Mika Watanabe
Teiji Tominaga
Publication date
01-09-2011
Publisher
Springer-Verlag
Published in
Child's Nervous System / Issue 9/2011
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-011-1485-y

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