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.
Similar content being viewed by others
References
Crawford JR, MacDonald TJ, Packer RJ (2007) Medulloblastoma in childhood: new biological advances. Lancet Neurol 6:1073–1085
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 24:167–176
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
Jakacki RI (2005) Treatment strategies for high-risk medulloblastoma and supratentorial primitive neuroectodermal tumors. Review of the literature. J Neurosurg 102(1 Suppl):44–52
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 33:817–823
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 46:269–279
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):1408–1414
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 24:4202–4208
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 17:2127–2136
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 74:433–440
Packer RJ, Vezina G (2008) Management of and prognosis with medulloblastoma: therapy at a crossroads. Arch Neurol 65:1419–1424
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 36:632–638
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 18:3004–3011
Acknowledgments
We thank Dr. Michael D. Taylor for providing the detailed methods for immunostaining with four antibodies: DKK1, SFRP1, NRP3, and KCNA1.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Saito, R., Kumabe, T., Sonoda, Y. et al. Combination chemotherapy with ifosfamide, cisplatin, and etoposide for medulloblastoma: single-institute experience and differences in efficacy for subgroups of medulloblastoma. Childs Nerv Syst 27, 1399–1406 (2011). https://doi.org/10.1007/s00381-011-1485-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00381-011-1485-y