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. 1996 Mar;74(3):219–223. doi: 10.1136/adc.74.3.219

An intensive multiagent chemotherapy regimen for brain tumours occurring in very young children.

L S Lashford 1, R H Campbell 1, H R Gattamaneni 1, K Robinson 1, D Walker 1, C Bailey 1
PMCID: PMC1511415  PMID: 8787426

Abstract

Standard treatment for the majority of malignant brain tumours consists of surgery and radiotherapy. This treatment has late morbidity which is accentuated in the very young child. As part of a strategy to improve quality of life and overall survival of young children with brain tumours, members of the United Kingdom Children's Cancer Study Group (UKCCSG) have piloted an intensive chemotherapy regimen which aims to avoid or delay radiotherapy following surgery. Twenty eight children with a variety of malignant brain tumours have received the regimen, which contains carboplatin, vincristine, cyclophosphamide, methotrexate, and cisplatin. The treatment is toxic, resulting in one death from infection. The bulk of the toxicity was associated with the administration of carboplatin. All but three children eventually required adjuvant radiotherapy and this was given between 1.5 and 27 months from diagnosis (median delay to radiotherapy, 12 months). Using this treatment regimen, overall survival at four years is 35% (confidence intervals 10% to 60%). While there is no evidence from this study that radiotherapy can be abandoned in the management of malignant brain tumours, its introduction may be delayed using suitable chemotherapy, thus allowing time for further CNS development. This treatment strategy has been taken forward as an international clinical trial run through the International Society for Paediatric Oncology, but using a smaller dose of carboplatin to reduce toxicity.

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Selected References

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  1. Allen J. C., Helson L. High-dose cyclophosphamide chemotherapy for recurrent CNS tumors in children. J Neurosurg. 1981 Nov;55(5):749–756. doi: 10.3171/jns.1981.55.5.0749. [DOI] [PubMed] [Google Scholar]
  2. Chin H. W., Maruyama Y. Recent progress and results of modern radiation therapy in medulloblastoma. Prog Clin Biol Res. 1983;130:401–410. [PubMed] [Google Scholar]
  3. Clayton P. E., Shalet S. M. Dose dependency of time of onset of radiation-induced growth hormone deficiency. J Pediatr. 1991 Feb;118(2):226–228. doi: 10.1016/s0022-3476(05)80487-1. [DOI] [PubMed] [Google Scholar]
  4. Clayton P. E., Shalet S. M. The evolution of spinal growth after irradiation. Clin Oncol (R Coll Radiol) 1991 Jul;3(4):220–222. doi: 10.1016/s0936-6555(05)80744-7. [DOI] [PubMed] [Google Scholar]
  5. Duffner P. K., Cohen M. E., Myers M. H., Heise H. W. Survival of children with brain tumors: SEER Program, 1973-1980. Neurology. 1986 May;36(5):597–601. doi: 10.1212/wnl.36.5.597. [DOI] [PubMed] [Google Scholar]
  6. Duffner P. K., Cohen M. E., Thomas P. R., Lansky S. B. The long-term effects of cranial irradiation on the central nervous system. Cancer. 1985 Oct 1;56(7 Suppl):1841–1846. doi: 10.1002/1097-0142(19851001)56:7+<1841::aid-cncr2820561325>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  7. Duffner P. K., Horowitz M. E., Krischer J. P., Friedman H. S., Burger P. C., Cohen M. E., Sanford R. A., Mulhern R. K., James H. E., Freeman C. R. Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med. 1993 Jun 17;328(24):1725–1731. doi: 10.1056/NEJM199306173282401. [DOI] [PubMed] [Google Scholar]
  8. Friedman H. S., Krischer J. P., Burger P., Oakes W. J., Hockenberger B., Weiner M. D., Falletta J. M., Norris D., Ragab A. H., Mahoney D. H., Jr Treatment of children with progressive or recurrent brain tumors with carboplatin or iproplatin: a Pediatric Oncology Group randomized phase II study. J Clin Oncol. 1992 Feb;10(2):249–256. doi: 10.1200/JCO.1992.10.2.249. [DOI] [PubMed] [Google Scholar]
  9. Gentet J. C., Doz F., Bouffet E., Plantaz D., Roché H., Tron P., Kalifa C., Mazingue F., Sariban E., Chastagner P. Carboplatin and VP 16 in medulloblastoma: a phase II Study of the French Society of Pediatric Oncology (SFOP). Med Pediatr Oncol. 1994;23(5):422–427. doi: 10.1002/mpo.2950230506. [DOI] [PubMed] [Google Scholar]
  10. Hirsch J. F., Renier D., Czernichow P., Benveniste L., Pierre-Kahn A. Medulloblastoma in childhood. Survival and functional results. Acta Neurochir (Wien) 1979;48(1-2):1–15. doi: 10.1007/BF01406016. [DOI] [PubMed] [Google Scholar]
  11. Horowitz M. E., Kun L. E., Mulhern R. K., Kovnar E. H., Sanford R. A., Hockenberger B. M., Greeson F. L., Langston J. W., Fairclough D. L., Jenkins J. J., 3rd Feasibility and efficacy of preirradiation chemotherapy for pediatric brain tumors. Neurosurgery. 1988 Apr;22(4):687–690. doi: 10.1227/00006123-198804000-00011. [DOI] [PubMed] [Google Scholar]
  12. Jenkin D., Goddard K., Armstrong D., Becker L., Berry M., Chan H., Doherty M., Greenberg M., Hendrick B., Hoffman H. Posterior fossa medulloblastoma in childhood: treatment results and a proposal for a new staging system. Int J Radiat Oncol Biol Phys. 1990 Aug;19(2):265–274. doi: 10.1016/0360-3016(90)90533-p. [DOI] [PubMed] [Google Scholar]
  13. Jenkin D., Goddard K., Armstrong D., Becker L., Berry M., Chan H., Doherty M., Greenberg M., Hendrick B., Hoffman H. Posterior fossa medulloblastoma in childhood: treatment results and a proposal for a new staging system. Int J Radiat Oncol Biol Phys. 1990 Aug;19(2):265–274. doi: 10.1016/0360-3016(90)90533-p. [DOI] [PubMed] [Google Scholar]
  14. Polednak A. P., Flannery J. T. Brain, other central nervous system, and eye cancer. Cancer. 1995 Jan 1;75(1 Suppl):330–337. doi: 10.1002/1097-0142(19950101)75:1+<330::aid-cncr2820751315>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  15. Porras-Ramírez G., Hernández-Herrera M. H., Porras-Hernández J. D. Amebic hepatic abscess in children. J Pediatr Surg. 1995 May;30(5):662–664. doi: 10.1016/0022-3468(95)90684-3. [DOI] [PubMed] [Google Scholar]
  16. Rosenstock J. G., Evans A. E., Schut L. Response to vincristine of recurrent brain tumors in children. J Neurosurg. 1976 Aug;45(2):135–140. doi: 10.3171/jns.1976.45.2.0135. [DOI] [PubMed] [Google Scholar]
  17. Schnabel A., Gross W. L. Low-dose methotrexate in rheumatic diseases--efficacy, side effects, and risk factors for side effects. Semin Arthritis Rheum. 1994 Apr;23(5):310–327. doi: 10.1016/0049-0172(94)90027-2. [DOI] [PubMed] [Google Scholar]
  18. Sexauer C. L., Khan A., Burger P. C., Krischer J. P., van Eys J., Vats T., Ragab A. H. Cisplatin in recurrent pediatric brain tumors. A POG Phase II study. A Pediatric Oncology Group Study. Cancer. 1985 Oct 1;56(7):1497–1501. doi: 10.1002/1097-0142(19851001)56:7<1497::aid-cncr2820560703>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
  19. Shapiro W. R., Young D. F., Mehta B. M. Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med. 1975 Jul 24;293(4):161–166. doi: 10.1056/NEJM197507242930402. [DOI] [PubMed] [Google Scholar]
  20. Smith M., Simon R. Age effects of radiation-associated neurotoxicity in children. J Clin Oncol. 1993 Jan;11(1):195–196. doi: 10.1200/JCO.1993.11.1.195. [DOI] [PubMed] [Google Scholar]
  21. Stiller C. A., Lennox E. L. Childhood medulloblastoma in Britain 1971-77: analysis of treatment and survival. Br J Cancer. 1983 Dec;48(6):835–841. doi: 10.1038/bjc.1983.274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Strauss L. C., Killmond T. M., Carson B. S., Maria B. L., Wharam M. D., Leventhal B. G. Efficacy of postoperative chemotherapy using cisplatin plus etoposide in young children with brain tumors. Med Pediatr Oncol. 1991;19(1):16–21. doi: 10.1002/mpo.2950190104. [DOI] [PubMed] [Google Scholar]
  23. Tait D. M., Thornton-Jones H., Bloom H. J., Lemerle J., Morris-Jones P. Adjuvant chemotherapy for medulloblastoma: the first multi-centre control trial of the International Society of Paediatric Oncology (SIOP I). Eur J Cancer. 1990 Apr;26(4):464–469. [PubMed] [Google Scholar]
  24. Walker R. W., Allen J. C. Cisplatin in the treatment of recurrent childhood primary brain tumors. J Clin Oncol. 1988 Jan;6(1):62–66. doi: 10.1200/JCO.1988.6.1.62. [DOI] [PubMed] [Google Scholar]

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