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Journal of Neuro-Oncology

, Volume 109, Issue 3, pp 565–571 | Cite as

Pilot study of systemic and intrathecal mafosfamide followed by conformal radiation for infants with intracranial central nervous system tumors: a pediatric brain tumor consortium study (PBTC-001)

  • Susan M. Blaney
  • Mehmet KocakEmail author
  • Amar Gajjar
  • Murali Chintagumpala
  • Thomas Merchant
  • Mark Kieran
  • Ian F. Pollack
  • Sri Gururangan
  • Russ Geyer
  • Peter Phillips
  • Roger E. McLendon
  • Roger Packer
  • Stewart Goldman
  • Anu Banerjee
  • Richard Heideman
  • James M. Boyett
  • Larry Kun
Clinical Study - Patient Study

Abstract

A pilot study to investigate the feasibility of the addition of intrathecal (IT) mafosfamide to a regimen of concomitant multi-agent systemic chemotherapy followed by conformal radiation therapy (RT) for children <3 years with newly diagnosed embryonal CNS tumors was performed. Ninety-three newly diagnosed infants and children (<3 years) with embryonal CNS tumors were enrolled. Twenty weeks of systemic multi-agent chemotherapy commenced within 35 days of surgery. Patients without CSF flow obstruction (n = 71) received IT mafosfamide (14 mg) with chemotherapy. Localized (M0) patients with SD or better subsequently received RT followed by 20 additional weeks of chemotherapy. Second look surgery was encouraged prior to RT if there was an incomplete surgical resection at diagnosis. 71 evaluable patients with normal CSF flow received IT Mafosfamide with systemic chemotherapy; patients with M + disease were removed from protocol therapy at 20 weeks and those with PD at the time of progression. One and 5-year progression free survival (PFS) and overall survival (OS) for the cohort of 71 evaluable patients were 52 ± 6.5 % and 33 ± 13 %, and 67 ± 6.2 % and 51 ± 11 %, respectively. The 1-year Progression Free Survival (PFS) for M0 patients with medulloblastoma (MB, n = 20), supratentorial primitive neuroectodermal tumor (PNET, n = 9), and atypical teratoid rhabdoid tumor (ATRT, n = 12) was 80 ± 7 %, 67 ± 15 % and 27 ± 13 % and 5-year PFS was 65 ± 19 %, 37 ± 29 %, and 0 ± 0 %, respectively. The addition of IT mafosfamide to systemic chemotherapy in infants with embryonal CNS tumors was feasible. The PFS for M0 patients appears comparable to or better than most prior historical comparisons and was excellent for those receiving conformal radiotherapy.

Keywords

Mafosfamide Intrathecal Infant brain tumor Embryonal CNS tumor Conformal radiation therapy 

Notes

Acknowledgments

The authors and the PBTC acknowledge administrative support of Ms. Dana Wallace and the clinical research assistant support of Mr. Joyson Pekkattil.

Funding

This work was supported in part by NIH CA-98-007 & NIH U01 CA81457, Bethesda, MD; Asta Medica, Frankfurt, Germany; and the American Lebanese Syrian Associated Charities, Memphis, TN.

Supplementary material

11060_2012_929_MOESM1_ESM.docx (123 kb)
Supplementary material 1 (DOCX 123 kb)

References

  1. 1.
    Duffner PK, Horowitz ME, Krischer JP et al (1993) Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med 328:1725–1731PubMedCrossRefGoogle Scholar
  2. 2.
    Rutkowski S, Bode U, Deinlein F et al (2005) Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med 352:978–986PubMedCrossRefGoogle Scholar
  3. 3.
    Walter AW, Mulhern RK, Gajjar A et al (1999) Survival and neurodevelopmental outcome of young children with medulloblastoma at St Jude Children’s Research Hospital. J Clin Oncol 17:3720–3728PubMedGoogle Scholar
  4. 4.
    Shalet SM, Beardwell CG, Pearson D et al (1976) The effect of varying doses of cerebral irradiation on growth hormone production in childhood. Clin Endocrinol 5:287–290CrossRefGoogle Scholar
  5. 5.
    Spunberg JJ, Chang CH, Goldman M et al (1981) Quality of long-term survival following irradiation for intracranial tumors in children under the age of two. Int J Radiat Oncol Biol Phys 7:727–736PubMedCrossRefGoogle Scholar
  6. 6.
    Mulhern RK, Hancock J, Fairclough D et al (1992) Neuropsychological status of children treated for brain tumors: a critical review and integrative analysis. Med Pediatr Oncol 20:181–191PubMedCrossRefGoogle Scholar
  7. 7.
    Rutkowski S, Gerber NU, von Hoff K et al (2009) Treatment of early childhood medulloblastoma by postoperative chemotherapy and deferred radiotherapy. Neuro Oncol 11:201–210PubMedCrossRefGoogle Scholar
  8. 8.
    Dhall G, Grodman H, Ji L et al (2008) Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the “Head Start” I and II protocols. Pediatr Blood Cancer 50:1169–1175PubMedCrossRefGoogle Scholar
  9. 9.
    Friedman HS, Colvin OM, Ludeman SM et al (1986) Experimental chemotherapy of human medulloblastoma with classical alkylators. Cancer Res 46:2827–2833PubMedGoogle Scholar
  10. 10.
    Friedman H, Mahaley S, Schold S et al (1986) Efficacy of vincristine and cyclophophamide in the therapy of recurrent medulloblastoma. Neurosurgery 18:335–340PubMedCrossRefGoogle Scholar
  11. 11.
    Allen J, Helson L (1981) High-dose cyclophosphamide chemotherapy for recurrent CNS tumors in children. J Neurosurg 55:749–756PubMedCrossRefGoogle Scholar
  12. 12.
    Jacob E, Scorsone K, Blaney SM et al (2008) Synergy of karenitecin and mafosfamide in pediatric leukemia, medulloblastoma, and neuroblastoma cell lines. Ped Blood Cancer 50:757–760CrossRefGoogle Scholar
  13. 13.
    Blaney SM, Boyett J, Friedman H et al (2005) Phase I clinical trial of mafosfamide in infants and children aged 3 years or younger with newly diagnosed embryonal tumors: a pediatric brain tumor consortium study (PBTC-001). J Clin Oncol 23:525–531PubMedCrossRefGoogle Scholar
  14. 14.
    Tan M, Xiong X (1996) Continuous and group sequential conditional probability ratio tests for phase II trials. Stastistics Med 15:2037–2051CrossRefGoogle Scholar
  15. 15.
    Geyer JR, Sposto R, Jennings M et al (2005) Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children’s Cancer Group. J Clin Oncol 23:7621–7631PubMedCrossRefGoogle Scholar
  16. 16.
    Rutkowski S, Cohen B, Finlay J et al (2010) Medulloblastoma in young children. Pediatric Blood Cancer 54:635–637PubMedCrossRefGoogle Scholar
  17. 17.
    Bandopadhayay P, Hassall TE, Rosenfeld JV et al (2011) ANZCCSG BabyBrain99; intensified systemic chemotherapy, second look surgery and involved field radiation in young children with central nervous system malignancy. Pediatric Blood Cancer 56:1055–1061PubMedCrossRefGoogle Scholar
  18. 18.
    McLendon RE, Adekunle A, Rajaram V, Koçak M, Blaney SM (2011) Embryonal central nervous system neoplasms arising in infants and young children: a pediatric brain tumor consortium study. Arch Pathol Lab Med 135:984–993PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Susan M. Blaney
    • 1
  • Mehmet Kocak
    • 2
    • 11
    Email author
  • Amar Gajjar
    • 2
  • Murali Chintagumpala
    • 1
  • Thomas Merchant
    • 2
  • Mark Kieran
    • 3
  • Ian F. Pollack
    • 4
  • Sri Gururangan
    • 5
  • Russ Geyer
    • 6
  • Peter Phillips
    • 7
  • Roger E. McLendon
    • 5
  • Roger Packer
    • 8
  • Stewart Goldman
    • 9
  • Anu Banerjee
    • 10
  • Richard Heideman
    • 2
    • 12
  • James M. Boyett
    • 2
  • Larry Kun
    • 2
  1. 1.Texas Children’s Cancer CenterBaylor College of MedicineHoustonUSA
  2. 2.St. Jude Children’s Research HospitalMemphisUSA
  3. 3.Dana-Farber Cancer Institute and Children’s Hospital BostonBostonUSA
  4. 4.Children’s Hospital of PittsburghPittsburghUSA
  5. 5.Duke University Medical CenterDurhamUSA
  6. 6.Children’s Hospital and Medical CenterSeattleUSA
  7. 7.Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  8. 8.Children’s National Medical CenterWashington, D.C.USA
  9. 9.Children’s Memorial HospitalChicagoUSA
  10. 10.University of CaliforniaSan FranciscoUSA
  11. 11.University of Tennessee Health Science CenterMemphisUSA
  12. 12.The University of New Mexico Health Sciences CenterAlbuquerqueUSA

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