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Treatments for Astrocytic Tumors in Children

Current and Emerging Strategies

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Abstract

Strategies for the treatment of childhood cancer have changed considerably during the last 50 years and have led to dramatic improvements in long-term survival. Despite these accomplishments, CNS tumors remain the leading cause of death in pediatric oncology. Astrocytic tumors form the most common histologic group among childhood brain tumors. They are a heterogeneous group that from a practical therapeutic point of view can be subdivided into low-grade astrocytomas (LGA), optic pathway gliomas (OPG), high-grade astrocytomas (HGA), and brainstem gliomas (BSG). This article focuses on the practical application of treatments that lead to long-term survival, improved quality of life, and reduced long-term complications.

Improvement in therapy has led to better outcomes for patients with LGA and OPG. Careful follow-up without any treatment is indicated for a small percentage of patients diagnosed with LGA with an indolent course including children with neurofibromatosis type 1 (NF1). Surgery is the main recommended treatment for children with resectable LGA. Radiation therapy is generally recommended for children with progressive LGA, or after failure of chemotherapy, accomplishing tumor control at 10 years in over 60% of patients. Cytotoxic chemotherapy is usually reserved for children who have had treatment failure with surgery and radiation therapy. It is also offered for children who are too young to be treated with radiation or to defer or avoid radiotherapy. Carboplatin and vincristine achieve 5% complete and 28% partial responses but the use of vincristine is criticized due to poor penetration of the CNS. A regimen of tioguanine, procarbazine, mitolactol, lomustine, and vincristine is frequently administered as an alternative to carboplatin and vincristine in LGA. The introduction of temozolomide has allowed better responses, including a 24% complete response rate compared with 0–5% complete response rates with the previous regimens. OPG are usually histologically LGA, and are treated with similar chemotherapy regimens. OPG is the most common type of brain tumor associated with NF1. Tumor growth in some of these patients is slow with no treatment recommended for an extended period of time.

The prognosis for children with the remaining types of astrocytomas remains poor. Surgical resection is typically the first step in the treatment of HGA followed in older children by radiation therapy. The data regarding chemotherapy are mixed. Combination chemotherapy before or after radiation, including cisplatin, carmustine, cyclophosphamide, and vincristine or carboplatin, ifosfamide, cyclophosphamide, and etoposide has provided disappointing results. Clinical trials with temozolomide and agents directed against single targets have not shown substantially better results, but it is hoped that currently conducted studies will provide better outcomes. Diffuse intrinsic BSG are among the most difficult-to-treat brain tumors. Surgical treatment is not recommended for diffuse intrinsic BSG and standard radiation therapy is typically given in children aged >3 years. None of the numerous chemotherapy regimens, including temozolomide, has provided a significant response rate or an improvement in survival. It is expected that newer agents affecting multiple targets such as AEE-788 and antineoplastons, and combinations of single-targeted agents with chemotherapy will provide better results.

Careful evaluation of histology, location of the tumor, patient age, and consideration of treatment-related morbidity play an important part in selecting between clinical observation, surgery, radiation, chemotherapy, or investigational agents. The goals of treatment for astrocytic tumors should extend well beyond objective responses and increased survival. Improvement of quality of life is an equally important objective of treatment. Radiation therapy and chemotherapy result in serious late toxicities.

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Table I
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References

  1. NCI. SEER cancer statistics review 1975–2001 [online]. Available from URL: http://seer.cancer.gov [Accessed 2006 May 19]

  2. Bleyer WA. Epidemiologic impact of children with brain tumors. Childs Nerv Syst 1999; 15: 758–63

    Article  PubMed  CAS  Google Scholar 

  3. CBTRUS. Statistical report: primary brain tumors in the United States, 1998–2002. Hindsale (IL): Central Brain Tumor Registry of the US (publishing assistance was provided by the Stromberg Allen Company), 2005

    Google Scholar 

  4. Kleihues P, Cavenee W. Pathology and genetics of tumors of the central nervous system. Lyon: International Agency for Research on Cancer, 1997

    Google Scholar 

  5. Reddy AT. Advances in biology and treatment of childhood brain tumors. Curr Neurol Neurosci Rep 2001; 1: 137–43

    Article  PubMed  CAS  Google Scholar 

  6. Zacharoulis S, Kieran MW. Treatment of low-grade gliomas in children: an update. Expert Rev Neurother 2004; 4: 1005–14

    Article  PubMed  Google Scholar 

  7. Reddy AT, Wellens JC. Pediatric high grade gliomas. In: Markert JM, editor. Glioblastoma multiforme. Boston (MA): Jones and Bartlett Publishers, 2005

    Google Scholar 

  8. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352: 987–96

    Article  PubMed  CAS  Google Scholar 

  9. DeAngelis LM. Chemotherapy for brain tumors: a new beginning. N Engl J Med 2005; 352: 1036–8

    Article  PubMed  CAS  Google Scholar 

  10. Lashford LS, Thiesse P, Jouvet A, et al. Temozolomide in malignant gliomas of childhood: a United Kingdom Children’s Cancer Study Group and French Society for Pediatric Oncology Intergroup Study. J Clin Oncol 2002; 20: 4684–91

    Article  PubMed  CAS  Google Scholar 

  11. Estlin EJ, Lashford L, Ablett S, et al. Phase I study of temozolomide in paediatric patients with advanced cancer: United Kingdom Children’s Cancer Study Group. Br J Cancer 1998; 78: 652–61

    Article  PubMed  CAS  Google Scholar 

  12. Burzynski SR. Targeted therapy for brain tumors. In: Columbus F, editor. Brain cancer research: progress. New York: Nova Science Publishers Inc, 2005

    Google Scholar 

  13. Lau CC. Genomic profiling in pediatric brain tumors. Cancer J 2005; 11: 283–93

    Article  PubMed  CAS  Google Scholar 

  14. Rubin JB, Gutmann DH. Neurofibromatosis type 1: a model for nervous system tumour formation? Nat Rev Cancer 2005; 5: 557–64

    Article  PubMed  CAS  Google Scholar 

  15. Pollack IF. Brain tumors in children. N Engl J Med 1994; 331: 1500–7

    Article  PubMed  CAS  Google Scholar 

  16. Korf BR. Diagnosis and management of neurofibromatosis type 1. Curr Neurol Neurosci Rep 2001; 1: 162–7

    Article  PubMed  CAS  Google Scholar 

  17. Zizka J, Elias P, Jakubec J. Spontaneous regression of low-grade astrocytomas: an underrecognized condition? Eur Radiol 2001; 11: 2638–40

    Article  PubMed  CAS  Google Scholar 

  18. Shaw EG, Wisoff JH. Prospective clinical trials of intracranial low-grade glioma in adults and children. Neuro-oncol 2003; 5: 153–60

    Article  PubMed  Google Scholar 

  19. Pollack IF, Pang D, Albright AL. The long-term outcome in children with late-onset aqueductal stenosis resulting from benign intrinsic tectal tumors. J Neurosurg 1994; 80: 681–8

    Article  PubMed  CAS  Google Scholar 

  20. Bowers DC, Georgiades C, Aronson LJ, et al. Tectal gliomas: natural history of an indolent lesion in pediatric patients. Pediatr Neurosurg 2000; 32: 24–9

    Article  PubMed  CAS  Google Scholar 

  21. Fisher BJ, Leighton CC, Vujovic O, et al. Results of a policy of surveillance alone after surgical management of pediatric low grade gliomas. Int J Radiat Oncol Biol Phys 2001; 51: 704–10

    Article  PubMed  CAS  Google Scholar 

  22. Kilic T, Ozduman K, Elmaci I, et al. Effect of surgery on tumor progression and malignant degeneration in hemispheric diffuse low-grade astrocytomas. J Clin Neurosci 2002; 9: 549–52

    Article  PubMed  Google Scholar 

  23. Saran FH, Baumert BG, Khoo VS, et al. Stereotactically guided conformal radiotherapy for progressive low-grade gliomas of childhood. Int J Radiat Oncol Biol Phys 2002; 53: 43–51

    Article  PubMed  Google Scholar 

  24. Merchant TE, Zhu Y, Thompson SJ, et al. Preliminary results from a phase II trial of conformal radiation therapy for pediatric patients with localised low-grade astrocytoma and ependymoma. Int J Radiat Oncol Biol Phys 2002; 52: 325–32

    Article  PubMed  Google Scholar 

  25. Marcus KJ. Stereotactic radiotherapy for localized LGGs in children: final results of a prospective trial. Int J Radiat Oncol Biol Phys 2005; 61: 374–9

    Article  PubMed  Google Scholar 

  26. Freeman CR, Bourgouin PM, Sanford RA, et al. Long term survivors of childhood brain stem gliomas treated with hyperfractionated radiotherapy: clinical characteristics and treatment related toxicities. The Pediatric Oncology Group. Cancer 1996; 77: 555–62

    Article  PubMed  CAS  Google Scholar 

  27. Lesser GJ. Chemotherapy of low-grade gliomas. Semin Radiat Oncol 2001; 11: 138–44

    Article  PubMed  CAS  Google Scholar 

  28. Massimino M, Spreafico F, Cefalo G, et al. High response rate to cisplatin/etoposide regimen in childhood low-grade glioma. J Clin Oncol 2002; 20: 4209–16

    Article  PubMed  CAS  Google Scholar 

  29. Rosenstock JG, Packer RJ, Bilaniuk L, et al. Chiasmatic optic glioma treated with chemotherapy: a preliminary report. J Neurosurg 1985; 63: 862–6

    Article  PubMed  CAS  Google Scholar 

  30. Lefkowitz IB, Packer RJ, Sutton LN, et al. Results of the treatment of children with recurrent gliomas with lomustine and vincristine. Cancer 1988; 61: 896–902

    Article  PubMed  CAS  Google Scholar 

  31. Bouffet E, Goldman S, Jakacki R, et al. Pilot study of vinblastine in patients with recurrent and refractory low-grade glioma [abstract]. Neuro-oncol 2004; 6: 450

    Google Scholar 

  32. Gururangan S, Allen JC, Phillips PC, et al. Phase II study of oral temozolomide (TMZ) in children with progressive low-grade gliomas (LGG) [abstract]. Neuro-oncol 2004; 6: 457

    Google Scholar 

  33. Quinn JA, Reardon DA, Friedman AH, et al. Phase II trial of temozolomide in patients with progressive low-grade glioma. J Clin Oncol 2003; 21: 646–51

    Article  PubMed  CAS  Google Scholar 

  34. Kuo DJ, Weiner HL, Wisoff J, et al. Temozolomide is active in childhood, progressive, unresectable, low-grade gliomas. J Pediatr Hematol Oncol 2003; 25: 372–8

    Article  PubMed  Google Scholar 

  35. Walter AW, Gajjar A, Reardon DA, et al. Tamoxifen and carboplatin for children with low-grade gliomas: a pilot study at St. Jude Children’s Research Hospital. J Pediatr Hematol Oncol 2000; 22: 247–51

    Article  PubMed  CAS  Google Scholar 

  36. Packer RJ, Ater J, Allen J, et al. Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas. J Neurosurg 1997; 86: 747–54

    Article  PubMed  CAS  Google Scholar 

  37. Pons MA, Finlay JL, Walker RW, et al. Chemotherapy with vincristine (VCR) and etoposide (VP-16) in children with low-grade astrocytoma. J Neurooncol 1992; 14: 151–8

    Article  PubMed  CAS  Google Scholar 

  38. Petronio J, Edwards MS, Prados M, et al. Management of chiasmal and hypothalamic gliomas of infancy and childhood with chemotherapy. J Neurosurg 1991; 74: 701–8

    Article  PubMed  CAS  Google Scholar 

  39. Burzynski SR. Clinical application of body epigenetic system: multi-targeted therapy for primary brain tumors. World and Ehrlich Conference on Dosing of Magic Bullets; 2004 Sep 9–11; Nürnberg

  40. Lafay-Cousin L, Holm S, Qaddoumi I, et al. Weekly vinblastine in pediatric low-grade glioma patients with carboplatin allergic reaction. Cancer 2005; 103: 2636–42

    Article  PubMed  CAS  Google Scholar 

  41. Edwards MS, Cogen PH. Craniospinal neoplasms, child neurology: a clinical manual. 2nd ed. Philadelphia (PA): JB Lippincott, 1994: 165–83

    Google Scholar 

  42. Dosoretz DE, Blitzer PH, Wang CC, et al. Management of glioma of the optic nerve and/or chiasm: an analysis of 20 cases. Cancer 1980; 45: 1467–71

    Article  PubMed  CAS  Google Scholar 

  43. Tenny RT, Laws Jr ER, Younge BR, et al. The neurosurgical management of optic glioma: results in 104 patients. J Neurosurg 1982; 57: 452–8

    Article  PubMed  CAS  Google Scholar 

  44. Janss AJ, Grundy R, Cnaan A, et al. Optic pathway and hypothalamic/chiasmatic gliomas in children younger than age 5 years with a 6-year follow-up. Cancer 1995; 75: 1051–9

    Article  PubMed  CAS  Google Scholar 

  45. Lewis RA, Gerson LP, Axelson KA, et al. von Recklinghausen neurofibromatosis: II. Incidence of optic gliomata. Ophthalmology 1984; 91: 929–35

    PubMed  CAS  Google Scholar 

  46. Riccardi VM. Type 1 neurofibromatosis and the pediatric patient. Curr Probl Pediatr 1992; 22: 66–106

    Article  PubMed  CAS  Google Scholar 

  47. Wisoff JH, Abbott R, Epstein F. Surgical management of exophytic chiasmatic-hypothalamic tumors of childhood. J Neurosurg 1990; 73: 661–7

    Article  PubMed  CAS  Google Scholar 

  48. Grabenbauer GG, Schuchardt U, Buchfelder M, et al. Radiation therapy of opticohypothalamic gliomas (OHG): radiographic response, vision and late toxicity. Radiother Oncol 2000; 54: 239–45

    Article  PubMed  CAS  Google Scholar 

  49. Kortmann RD, Timmermann B, Taylor RE, et al. Current and future strategies in radiotherapy of childhood low-grade glioma of the brain: part I. Treatment modalities of radiation therapy. Strahlenther Onkol 2003; 179: 509–20

    Article  PubMed  Google Scholar 

  50. Packer RJ, Sutton LN, Bilaniuk LT, et al. Treatment of chiasmatic/hypothalamic gliomas of childhood with chemotherapy: an update. Ann Neurol 1988; 23: 79–85

    Article  PubMed  CAS  Google Scholar 

  51. Gnekow AK, Kortmann RD, Pietsch T, et al. 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. Society of Pediatric Oncology and Hematology (GPOH). Klin Padiatr 2004; 216: 331–42

    Article  PubMed  CAS  Google Scholar 

  52. Burzynski SR. Methods for treating neurofibromatosis. U.S. Patent No. 5391575 (issued 1995)

  53. Geyer JR. Gliomas in the very young child. In: Berger MS, Wilson CB, editors. The gliomas. Philadelphia (PA): WB Saunders Co, 1999

    Google Scholar 

  54. Marchese MJ, Chang CH. Malignant astrocytic gliomas in children. Cancer 1990; 65: 2771–8

    Article  PubMed  CAS  Google Scholar 

  55. Conway PD, Oechler HW, Kun LE, et al. Importance of histologic condition and treatment of pediatric cerebellar astrocytoma. Cancer 1991; 67: 2772–5

    Article  PubMed  CAS  Google Scholar 

  56. Wisoff JH, Boyett JM, Berger MS, et al. Current neurosurgical management and the impact of the extent of resection in the treatment of malignant gliomas of childhood: a report of the Children’s Cancer Group trial no. CCG-945. J Neurosurg 1998; 89: 52–9

    Article  PubMed  CAS  Google Scholar 

  57. Heideman RL, Kuttesch Jr J, Gajjar AJ, et al. Supratentorial malignant gliomas in childhood: a single institution perspective. Cancer 1997; 80: 497–504

    Article  PubMed  CAS  Google Scholar 

  58. Packer RJ, Boyett JM, Zimmerman RA, et al. Outcome of children with brain stem gliomas after treatment with 7800 cGy of hyperfractionated radiotherapy: a Children’s Cancer Group phase I/II trial. Cancer 1994; 74: 1827–34

    Article  PubMed  CAS  Google Scholar 

  59. Hodgson DC, Goumnerova LC, Loeffler JS, et al. Radiosurgery in the management of pediatric brain tumors. Int J Radiat Oncol Biol Phys 2001; 50: 929–35

    Article  PubMed  CAS  Google Scholar 

  60. Dropcho EJ, Wisoff JH, Walker RW, et al. Supratentorial malignant gliomas in childhood: a review of fifty cases. Ann Neurol 1987; 22: 355–64

    Article  PubMed  CAS  Google Scholar 

  61. Sposto R, Ertel IJ, Jenkin RDT, et al. The effectiveness of chemotherapy for treatment of high grade astrocytoma in children: results of a randomized trial. A report from the Children’s Cancer Study Group. J Neurooncol 1989; 7: 165–77

    Article  PubMed  CAS  Google Scholar 

  62. Finlay JL, Boyett JM, Yates AJ, et al. Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen: Children’s Cancer Group. J Clin Oncol 1995; 13: 112–23

    PubMed  CAS  Google Scholar 

  63. Boyett J, Yates A, Gilles F, et al. When is a high-grade astrocytoma (HGA) not a HGA? Results of a central review of 226 cases of anaplastic astrocytoma (AA), glioblastoma multiforme (GBM), and other HGA (OTH-HGA) by five neuropathologists [abstract]. Proc Soc Clin Oncol 1998; 17: 526

    Google Scholar 

  64. Chintagumpala M, Burger P, McCluggage CW. DNA mismatch repair and 06-alkyguanine-DNA alkyltransferase (AGT analysis and response to procarbazine in malignant glioma in children: a Pediatric Oncology Group (POG) study [abstract]. Med Pediatr Oncol 1999; 22: 159

    Google Scholar 

  65. Chintagumpala M, Steward C, Burger P. Response to topotecan in newly diagnosed patients with high-grade gliomas: a Pediatric Oncology Group (POG) study. 9th International Symposium on Pediatric Neuro-Oncology; 2000 Jun 11–14; San Francisco (CA)

  66. Arenson E, Ater J, Bank J, et al. A randomized phase II trial of high dose alkylating agents plus VP-16 in children with high-grade astrocytoma [abstract]. J Pediatr Hematol Oncol 1999; 21: 325

    Article  Google Scholar 

  67. Jakacki RI, Siffert J, Jamison C, et al. Dose-intensive, time-compressed procarbazine, CCNU, vincristine (PCV) with peripheral blood stem cell support and concurrent radiation in patients with newly diagnosed high-grade gliomas. J Neurooncol 1999; 44: 77–83

    Article  PubMed  CAS  Google Scholar 

  68. Huncharek M, Wheeler L, McGarry R, et al. Chemotherapy response rates in recurrent/progressive pediatric glioma: results of a systematic review. Anti-cancer Res 1999; 19: 3569–74

    CAS  Google Scholar 

  69. Nicholson HS, Krailo M, Ames MM, et al. Phase I study of temozolomide in children and adolescents with recurrent solid tumors: a report from the Children’s Cancer Group. J Clin Oncol 1998; 16: 3037–43

    PubMed  CAS  Google Scholar 

  70. Korones DN, Smith AA, Bouffet E, et al. Temozolomide and oral VP-16 for children and young adults with recurrent or secondary malignant brain tumors [abstract]. Neuro-oncol 2004; 6: 460

    Google Scholar 

  71. Broniscer A, Chintagumpala M, Bowers DC, et al. Upfront protracted irinotecan (CPT-11) followed by radiotherapy (RT) and temozolomide (TMZ) in the treatment of children with newly diagnosed high-grade glioma (HGG) and unfavorable low-grade glioma (LGG): results of a multi-institutional study (SJHG-98) [abstract]. Neuro-oncol 2004; 6: 385

    Google Scholar 

  72. Freeman CR, Farmer JP. Pediatric brain stem gliomas: a review. Int J Radiat Oncol Biol Phys 1998; 40: 265–71

    Article  PubMed  CAS  Google Scholar 

  73. Pollack IF, Shultz B, Mulvihill JJ. The management of brainstem gliomas in patients with neurofibromatosis 1. Neurology 1996; 46: 1652–60

    Article  PubMed  CAS  Google Scholar 

  74. Guillamo JS, Doz F, Delattre JY. Brain stem gliomas. Curr Opin Neurol 2001; 14: 711–5

    Article  PubMed  CAS  Google Scholar 

  75. Cheng Y, Ng HK, Zhang SF, et al. Genetic alterations in pediatric high-grade astrocytomas. Hum Pathol 1999; 30: 1284–90

    Article  PubMed  CAS  Google Scholar 

  76. Louis DN, Rubio MP, Correa KM, et al. Molecular genetics of pediatric brain stem gliomas: application of PCR techniques to small and archival brain tumor specimens. J Neuropathol Exp Neurol 1993; 52: 507–15

    Article  PubMed  CAS  Google Scholar 

  77. Gilbertson RJ, Hill DA, Hernan R, et al. ERBB1 is amplified and overexpressed in high-grade diffusely infiltrative pediatric brain stem glioma. Clin Cancer Res 2003; 9: 3620–4

    PubMed  CAS  Google Scholar 

  78. Mandell LR, Kadota R, Freeman C, et al. There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brainstem tumors: results of a Pediatric Oncology Group phase III trial comparing conventional vs. hyperfractionated radiotherapy. Int J Radiat Oncol Biol Phys 1999; 43: 959–64

    Article  PubMed  CAS  Google Scholar 

  79. Broniscer A, Gajjar A. Supratentorial high-grade astrocytoma and diffuse brainstem glioma: two challenges for the pediatric oncologist. Oncologist 2004; 9: 197–206

    Article  PubMed  Google Scholar 

  80. Allen J, Siffert J, Donahue B, et al. A phase I/II study of carboplatin combined with hyperfractionated radiotherapy for brainstem gliomas. Cancer 1999; 86: 1064–9

    Article  PubMed  CAS  Google Scholar 

  81. Freeman CR, Perilongo G. Chemotherapy for brain stem gliomas. Childs Nerv Syst 1999; 15: 545–53

    Article  PubMed  CAS  Google Scholar 

  82. Freeman CR, Kepner J, Kun LE, et al. A detrimental effect of a combined chemotherapy-radiotherapy approach in children with diffuse intrinsic brain stem gliomas? Int J Radiat Oncol Biol Phys 2000; 47: 561–4

    Article  PubMed  CAS  Google Scholar 

  83. Broniscer A, Leite CC, Lanchote VL, et al. Radiation therapy and high-dose tamoxifen in the treatment of patients with diffuse brainstem gliomas: results of a Brazilian cooperative study. Brainstem Glioma Cooperative Group. J Clin Oncol 2000; 18: 1246–53

    PubMed  CAS  Google Scholar 

  84. Jennings MT, Sposto R, Boyett JM, et al. Preradiation chemotherapy in primary high-risk brainstem tumors: phase II study CCG-9941 of the Children’s Cancer Group. J Clin Oncol 2002; 20: 3431–7

    Article  PubMed  CAS  Google Scholar 

  85. Massimino M, Gandola L, Spreafico F, et al. Intrinsic brain stem tumor: changing strategies, changing results? [abstract]. Neuro-oncol 2003; 5: 51

    Google Scholar 

  86. Broniscer A, Iacono L, Chintagumpala M, et al. Role of temozolomide after radiotherapy for newly diagnosed diffuse brainstem glioma in children: results of a multiinstitutional study (SJHG-98). Cancer 2005; 103: 133–9

    Article  PubMed  CAS  Google Scholar 

  87. Bouffet E, Raquin M, Doz F, et al. Radiotherapy followed by high dose busulfan and thiotepa: a prospective assessment of high dose chemotherapy in children with diffuse pontine gliomas. Cancer 2000; 88: 685–92

    Article  PubMed  CAS  Google Scholar 

  88. Burzynski SR, Weaver RA, Janicki T. Long-term survival in phase II studies of antineoplastons A10 and AS2-1 (ANP) in patients with diffuse intrinsic brain stem glioma [abstract]. Neuro-oncol 2004; 6: 386

    Google Scholar 

  89. Burzynski SR, Weaver RA, Janicki TJ, et al. Targeted therapy with ANP in children less than 4 years old with inoperable brain stem gliomas [abstract]. Neuro-oncol 2005; 7: 300

    Google Scholar 

  90. Burzynski SR, Lewy RI, Weaver RA, et al. Phase II study of antineoplaston A10 and AS2-1 in patients with recurrent diffuse intrinsic brain stem glioma: a preliminary report. Drugs R D 2003; 4: 91–101

    Article  PubMed  CAS  Google Scholar 

  91. Burzynski SR, Weaver RA, Janicki T, et al. Targeted therapy with antineoplastons A10 and AS2-1 (ANP) of high-grade, recurrent and progressive brain stem glioma. Integr Cancer Ther 2006 Mar; 5(1): 40–7

    Article  PubMed  CAS  Google Scholar 

  92. Sheline GE, Wara WM, Smith V. Therapeutic irradiation and brain injury. Int J Radiat Oncol Biol Phys 1980; 6: 1215–28

    Article  PubMed  CAS  Google Scholar 

  93. Nelson DF, Curran Jr WJ, Scott C, et al. Hyperfractionated radiation therapy and bis-chlorethyl nitrosourea in the treatment of malignant glioma: possible advantage observed at 72.0 Gy in 1.2 Gy B.I.D. fractions. Report of the Radiation Therapy Oncology Group Protocol 8302. Int J Radiat Oncol Biol Phys 1993; 25: 193–207

    Article  PubMed  CAS  Google Scholar 

  94. Marks JE, Baglan RJ, Prassad SC, et al. Cerebral radionecrosis: incidence and risk in relation to dose, time, fractionation and volume. Int J Radiat Oncol Biol Phys 1981; 7: 243–52

    Article  PubMed  CAS  Google Scholar 

  95. Bleyer WA, Griffin TW. White matter necrosis, microangiopathy and intellectual abilities in survivors of childhood leukemia: association with central nervous system irradiation and methotrexate therapy. In: Gilbert HA, Kagan AR, editors. Radiation damage to the nervous system. New York: Raven, 1980

    Google Scholar 

  96. Lee YY, Nauert C, Glass JP. Treatment-related white matter changes in cancer patients. Cancer 1986; 57: 1473–82

    Article  PubMed  CAS  Google Scholar 

  97. Styopoulos LA, George AE, de Leon MJ. Longitudinal CT study of parenchymal brain changes in glioma survivors. AJNR Am J Neuroradiol 1988 May–Jun; 9(3): 517–22

    Google Scholar 

  98. Parsons JT, Bova FJ, Fitzgerald CR, et al. Radiation optic neuropathy after megavoltage external-beam irradiation: analysis of time-dose factors. Int J Radiat Oncol Biol Phys 1994; 30: 755–63

    Article  PubMed  CAS  Google Scholar 

  99. Goldsmith BJ, Rosenthal SA, Wara WM, et al. Optic neuropathy after irradiation of meningioma. Radiology 1992; 185: 71–6

    PubMed  CAS  Google Scholar 

  100. Cavazzuti V, Winston K, Baker R, et al. Psychological changes following surgery for tumors in the temporal lobe. J Neurosurg 1980; 53: 618–26

    Article  PubMed  CAS  Google Scholar 

  101. Riva D, Pantaleoni C, Milani N, et al. Impairment of neuropsychological functions in children with medulloblastomas and astrocytomas in the posterior fossa. Childs Nerv Syst 1989; 5: 107–10

    Article  PubMed  CAS  Google Scholar 

  102. Carpentieri S, Mulhern RK, Douglas SM. Behavioral resiliency among children surviving brain tumors: a longitudinal study. J Clin Child Psychol 1994; 22: 236–46

    Article  Google Scholar 

  103. Mostow EN, Byrne J, Connelly RR, et al. Quality of life in long-term survivors of CNS tumors of childhood and adolescence. J Clin Oncol 1991; 9: 592–9

    PubMed  CAS  Google Scholar 

  104. Bloom HJ, Wallace EN, Henk JM. The treatment and prognosis of medulloblastoma in children: a study of 82 verified cases. Am J Roentgenol Radium Ther Nucl Med 1969; 105: 43–62

    PubMed  CAS  Google Scholar 

  105. Shalet SM. Irradiation-induced growth failure. Clin Endocrinol Metab 1986; 15: 591–606

    Article  PubMed  CAS  Google Scholar 

  106. Park TS, Hoffman HJ, Hendrick EB, et al. Medulloblastoma: clinical presentation and management. Experience at the Hospital for Sick Children, Toronto, 1950–1980. J Neurosurg 1983; 58: 543–52

    Article  PubMed  CAS  Google Scholar 

  107. Haider A, Cullen JW, Eilerbeck JA. Pituitary function in children and adolescents following treatment for glial tumors. J Pediatr Oncol 1989; 3: 205–11

    Google Scholar 

  108. Oberfield SE, Allen JC, Pollack J, et al. Long-term endocrine sequelae after treatment of medulloblastoma: prospective study of growth and thyroid function. J Pediatr 1986; 108: 219–23

    Article  PubMed  CAS  Google Scholar 

  109. Rappaport R, Brauner R. Growth and endocrine disorders secondary to cranial irradiation. Pediatr Res 1989; 25: 561–7

    Article  PubMed  CAS  Google Scholar 

  110. Mack EE. Radiation-induced tumors. In: Berger MS, Wilson CB, editors. The gliomas. Philadelphia (PA): WB Saunders, 1999

    Google Scholar 

  111. Meadows AT, D’Angio GJ, Mike V, et al. Patterns of second malignant neoplasms in children. Cancer 1977; 40: 1903–11

    Article  PubMed  CAS  Google Scholar 

  112. Neglia JP, Meadows AT, Robison LL, et al. Second neoplasms after acute lymphoblastic leukemia in childhood. N Engl J Med 1991; 325: 1330–6

    Article  PubMed  CAS  Google Scholar 

  113. Kingston JE, Hawkins MM, Draper GJ, et al. Patterns of multiple primary tumours in patients treated for cancer during childhood. Br J Cancer 1987; 56: 331–8

    Article  PubMed  CAS  Google Scholar 

  114. Hawkins MM, Draper GJ, Kingston JE. Incidence of second primary tumours among childhood cancer survivors. Br J Cancer 1987; 56: 339–47

    Article  PubMed  CAS  Google Scholar 

  115. Duffner PK, Horowitz ME, Krischer JP, et al. Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med 1993; 328: 1725–31

    Article  PubMed  CAS  Google Scholar 

  116. De Vita VT, Carbone PP, Owens AHJ. Clinical trials with 1.3-bis(2-chloroethyl)-1-nitrosourea, NSC-409962. Cancer Res 1965; 25: 1876–81

    PubMed  Google Scholar 

  117. Kumar L, Dua H. Cis-platin induced anaemia [letter]. N Z Med J 1987; 100: 81

    PubMed  CAS  Google Scholar 

  118. Calvert AH, Newell DR, Gore ME. Future directions with carboplatin: can therapeutic monitoring, high-dose administration, and hematologic support with growth factors expand the spectrum compared with cisplatin? Semin Oncol 1992; 19: 155–63

    PubMed  CAS  Google Scholar 

  119. Rivkees SA, Crawford JD. The relationship of gonadal activity and chemotherapy-induced gonadal damage. JAMA 1988; 259: 2123–5

    Article  PubMed  CAS  Google Scholar 

  120. Parvinen LM. Early effects of procarbazine (N-isopropyl-L-(2-methylhydrazino)-p-toluamide hydrochloride) on rat spermatogenesis. Exp Mol Pathol 1979; 30: 1–11

    Article  PubMed  CAS  Google Scholar 

  121. Roth BJ, Einhorn LH, Greist A. Long-term complications of cisplatin-based chemotherapy for testis cancer. Semin Oncol 1988; 15: 345–50

    PubMed  CAS  Google Scholar 

  122. Clayton PE, Shalet SM, Price DA, et al. Ovarian function following chemotherapy for childhood brain tumours. Med Pediatr Oncol 1989; 17: 92–6

    Article  PubMed  CAS  Google Scholar 

  123. Schilsky RL, Sherins RJ, Hubbard SM, et al. Long-term follow up of ovarian function in women treated with MOPP chemotherapy for Hodgkin’s disease. Am J Med 1981; 71: 552–6

    Article  PubMed  CAS  Google Scholar 

  124. Goren MP, Wright RK, Horowitz ME. Cumulative renal tubular damage associated with cisplatin nephrotoxicity. Cancer Chemother Pharmacol 1986; 18: 69–73

    Article  PubMed  CAS  Google Scholar 

  125. Schact RG, Baldwin DS. Chronic interstitial nephritis and renal failure due to nitrosourea therapy [letter]. Kidney Int 1978; 14: 661

    Google Scholar 

  126. Dobyan DC, Levi J, Jacobs C, et al. Mechanism of cis-platinum nephrotoxicity: II. Morphologic observations. J Pharmacol Exp Ther 1980; 213: 551–6

    PubMed  CAS  Google Scholar 

  127. Holoye PY, Jenkins DE, Greenberg SD. Pulmonary toxicity in long-term administration of BCNU. Cancer Treat Rep 1976; 60: 1691–4

    PubMed  CAS  Google Scholar 

  128. Jones SE, Moore M, Blank N, et al. Hypersensitivity to procarbazine (Matulane) manifested by fever and pleuropulmonary reaction. Cancer 1972; 29: 498–500

    Article  PubMed  CAS  Google Scholar 

  129. Garbes ID, Henderson ES, Gomez GA, et al. Procarbazine-induced interstitial pneumonitis with a normal chest x-ray: a case report. Med Pediatr Oncol 1986; 14: 238–41

    Article  PubMed  CAS  Google Scholar 

  130. Grimson BS, Mahaley Jr MS, Dubey HD, et al. Ophthalmic and central nervous system complications following intracarotid BCNU (carmustine). J Clin Neuroophthalmol 1981; 1: 261–4

    Article  PubMed  CAS  Google Scholar 

  131. Shingleton BJ, Bienfang DC, Albert DM, et al. Ocular toxicity associated with high-dose carmustine. Arch Ophthalmol 1982; 100: 1766–72

    Article  PubMed  CAS  Google Scholar 

  132. Mahaley Jr MS, Whaley RA, Blue M, et al. Central neurotoxicity following intracarotid BCNU chemotherapy for malignant gliomas. J Neurooncol 1986; 3: 297–314

    Article  PubMed  Google Scholar 

  133. Kleinschmidt-DeMasters BK. Intracarotid BCNU leukoencephalopathy. Cancer 1986; 57: 1276–80

    Article  PubMed  CAS  Google Scholar 

  134. Rosenblum MK, Delattre JY, Walker RW, et al. Fatal necrotizing encephalopathy complicating treatment of malignant gliomas with intra-arterial BCNU and irradiation: a pathological study. J Neurooncol 1989; 7: 269–81

    Article  PubMed  CAS  Google Scholar 

  135. Weiss HD, Walker MD, Wiernik PH. Neurotoxicity of commonly used antineoplastic agents (second of two parts). N Engl J Med 1974; 291: 127–33

    Article  PubMed  CAS  Google Scholar 

  136. Roca E, Bruera E, Politi PM, et al. Vinca alkaloid-induced cardiovascular autonomic neuropathy. Cancer Treat Rep 1985; 69: 149–51

    PubMed  CAS  Google Scholar 

  137. von Hoff DD, Schilksy R, Reichert CM. Toxic effects of cisdiamminedichloroplatinum (II) in man. Cancer Treat Rep 1979; 63: 1527–31

    Google Scholar 

  138. Hansen SW, Helweg-Larsen S, Trojaborg W. Long-term neurotoxicity in patients treated with cisplatin, vinblastine, and bleomycin for metastatic germ cell cancer. J Clin Oncol 1989; 7: 1457–61

    PubMed  CAS  Google Scholar 

  139. Grunberg SM, Sonka S, Stevenson LL, et al. Progressive paresthesias after cessation of therapy with very high-dose cisplatin. Cancer Chemother Pharmacol 1989; 25: 62–4

    Article  PubMed  CAS  Google Scholar 

  140. Schaefer SD, Post JD, Close LG, et al. Ototoxicity of low- and moderate-dose cisplatin. Cancer 1985; 56: 1934–9

    Article  PubMed  CAS  Google Scholar 

  141. Mulhern RK, Ochs JJ, Kun LE. Changes in intellect associated with cranial radiation therapy. In: Gutin PH, Leibel SA, Sheline GE, editors. Radiation injury to the nervous system. New York: Raven, 1991

    Google Scholar 

  142. Greene MH, Boice Jr JD, Strike TA. Carmustine as a cause of acute nonlymphocytic leukemia [letter]. N Engl J Med 1985; 313: 579

    Article  PubMed  CAS  Google Scholar 

  143. Cohen RJ, Wiernik PH, Walker MD. Acute nonlymphocytic leukemia associated with nitrosourea chemotherapy: report of two cases. Cancer Treat Rep 1976; 60: 1257–61

    PubMed  CAS  Google Scholar 

  144. Pogliani EM, Pioltelli P, Rossini F, et al. Acute leukaemia following cisplatin for ovarian cancer. Haematologica 1987; 72: 184–5

    PubMed  CAS  Google Scholar 

  145. Bassett WB, Weiss RB. Acute leukemia following cisplatin for bladder cancer [letter]. J Clin Oncol 1986; 4: 614

    PubMed  CAS  Google Scholar 

  146. Des Guetz G. The 41st Annual ASCO Meeting: targeted therapies, Orlando, Florida. Targ Oncol 2006; 1: 59–65

    Article  Google Scholar 

  147. Burzynski SR. Annual report to the FDA, IND 43,742, 2006

  148. Zhou YH, Hess KR, Liu L, et al. Modeling prognosis for patients with malignant astrocytic gliomas: quantifying the expression of multiple genetic markers and clinical variables. Neuro-oncol 2005; 7: 485–94

    Article  PubMed  CAS  Google Scholar 

  149. Bast Jr RC, Hortobagyi GN. Individualized care for patients with cancer: a work in progress. N Engl J Med 2004; 351: 2865–7

    Article  PubMed  CAS  Google Scholar 

  150. Cohen KJ, Aronson LJ. Is there justification for the continued use of vincristine in pediatric brain tumor treatment? [abstract]. Neuro-oncol 2004; 6: 451

    Google Scholar 

  151. Oeffinger KC, Hudson MM. Long-term complications following childhood and adolescent cancer: foundations for providing risk-based health care for survivors. CA Cancer J Clin 2004; 54: 208–36

    Article  PubMed  Google Scholar 

  152. Bhatia S, Landier W. Evaluating survivors of pediatric cancer. Cancer J 2005; 11: 340–54

    Article  PubMed  Google Scholar 

  153. Leibel SA, Gutin PH, Wara WM, et al. Survival and quality of life after interstitial implantation of removable high-activity iodine-125 sources for the treatment of patients with recurring malignant gliomas. Int J Radiat Oncol Biol Phys 1989; 17: 1129–39

    Article  PubMed  CAS  Google Scholar 

  154. Wen PY, Alexander III E, Black PM, et al. Long term results of stereotactic brachytherapy used in the initial treatment of patients with glioblastomas. Cancer 1994; 73: 3029–36

    Article  PubMed  CAS  Google Scholar 

  155. Pollack I. Advances in the management of childhood gliomas: molecular markers of prognosis and novel treatment approaches [abstract]. Neuro-oncol 2005; 7: 348

    Google Scholar 

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Acknowledgments

No sources of funding were used to assist in the preparation of this review. Dr Burzynski is the President and Chairman of the Board of Directors of Burzynski Research Institute, Inc., which owns licenses for ANP in the US, Canada, and Mexico; and is a President of the Burzynski Clinic.

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Burzynski, S.R. Treatments for Astrocytic Tumors in Children. Pediatr-Drugs 8, 167–178 (2006). https://doi.org/10.2165/00148581-200608030-00003

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