Nitrogen mustard, vincristine, procarbazine, and prednisone as adjuvant chemotherapy in the treatment of medulloblastoma

A Pediatric Oncology Group study

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✓ In a randomized postoperative trial, adjuvant post-irradiation chemotherapy, consisting of nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP), was tested versus radiation therapy alone for newly diagnosed medulloblastoma in patients between 1 and 21 years of age. Patients treated with irradiation plus MOPP had a statistically significant increase in overall survival rate at 5 years posttreatment compared to patients treated with radiation therapy alone (74% vs. 56%; p = 0.06, adjusted for race and gender). Although the overall study failed to show a statistically significant advantage for irradiation plus MOPP in event-free survival (p = 0.18), statistical significance was attained in children 5 years of age or older (p = 0.05). More severe hematological toxicities occurred in the group with irradiation plus MOPP; however, this hematotoxicity appeared to be tolerable and acceptable. These results suggest that patients may benefit from combined irradiation and chemotherapy following surgery for medulloblastoma.

Article Information

Address for Dr. Krischer: University of Florida, Gainesville, Florida.

Address for Drs. Rajab and Kim: Emory University, Atlanta, Georgia.

Address for Dr. Kun: St. Jude Children's Research Hospital, Memphis, Tennessee.

Address for Dr. Laurent: Baylor College of Medicine, Houston, Texas.

Address for Dr. Boyett: The Cleveland Clinic Foundation, Cleveland, Ohio.

Address for Dr. Cornell: Dartmouth-Hitchcock Medical Center, Hanover, New Hampshire.

Address for Dr. Link: Stanford University Medical Center, Stanford, California.

Address for Dr. Luthy: Swiss Pediatric Oncology Group, Bern, Switzerland.

Address for Dr. Camitta: Midwest Children's Cancer Center, Milwuakee, Wisconsin.

Address reprint requests to: Jeffrey P. Krischer, Ph.D., Pediatric Oncology Group, Suite 2A, 4949 West Pine Boulevard, St. Louis. Missouri 63108.

© AANS, except where prohibited by US copyright law.

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Figures

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    Graph depicting the event-free survival rate of 35 patients receiving radiation therapy alone (broken line) and that of 36 patients receiving radiation therapy plus MOPP (solid line). Median survival rates have not been attained and the curves are not statistically different at p = 0.18. PROB = probability of event-free survival.

  • View in gallery

    Graph showing the overall survival rate of 35 patients receiving radiation therapy alone (broken line) and that of 36 patients receiving radiation therapy plus MOPP (solid line). Median survival rates have not been attained and the curves are significantly different at p = 0.055. PROB = probability of survival.

References

1.

Agresti AWackerly DBoyett JM: Exact conditional test for cross classifications: approximation of attained significance levels. Psychometrika 44:75831979Agresti A Wackerly D Boyett JM: Exact conditional test for cross classifications: approximation of attained significance levels. Psychometrika 44:75–83 1979

2.

Bailey CC: Brain tumors in childhood. Recent Results Cancer Res 88:64681983Bailey CC: Brain tumors in childhood. Recent Results Cancer Res 88:64–68 1983

3.

Berry MPJenkin RDTKeen CWet al: Radiation treatment for medulloblastoma. A 21-year review. J Neurosurg 55:43511981Berry MP Jenkin RDT Keen CW et al: Radiation treatment for medulloblastoma. A 21-year review. J Neurosurg 55:43–51 1981

4.

Bertolone SJBaum ESKrivit Wet al: A Phase II study of cisplatin therapy in recurrent childhood brain tumors. A report from the Childrens Cancer Study Group. J Neurooncol 7:5111989Bertolone SJ Baum ES Krivit W et al: A Phase II study of cisplatin therapy in recurrent childhood brain tumors. A report from the Childrens Cancer Study Group. J Neurooncol 7:5–11 1989

5.

Bloom HJG: Intracranial tumors: response and resistance to therapeutic endeavors, 1970–1980. Int J Radiat Oncol Biol Phys 8:108311131982Bloom HJG: Intracranial tumors: response and resistance to therapeutic endeavors 1970–1980. Int J Radiat Oncol Biol Phys 8:1083–1113 1982

6.

Bloom HJG: Medulloblastoma in children: increasing survival rates and future prospects. Int J Radiat Oncol Biol Phys 8:202320271982Bloom HJG: Medulloblastoma in children: increasing survival rates and future prospects. Int J Radiat Oncol Biol Phys 8:2023–2027 1982

7.

Cangir ARagab AHSteuber Pet al: Combination chemotherapy with vincristine (NSC-67574), procarbazine (NSC-77213), prednisone (NSC-10023) with and without nitrogen mustard (NSC-762) (MOPP vs OPP) in children with recurrent brain tumors. Med Pediatr Oncol 12:131984Cangir A Ragab AH Steuber P et al: Combination chemotherapy with vincristine (NSC-67574) procarbazine (NSC-77213) prednisone (NSC-10023) with and without nitrogen mustard (NSC-762) (MOPP vs OPP) in children with recurrent brain tumors. Med Pediatr Oncol 12:1–3 1984

8.

Chamberlain MCSilver PEdwards MSBet al: Treatment of extraneural metastatic medulloblastoma with a combination of cyclophosphamide, adriamycin, and vincristine. Neurosurgery 23:4764791988Chamberlain MC Silver P Edwards MSB et al: Treatment of extraneural metastatic medulloblastoma with a combination of cyclophosphamide adriamycin and vincristine. Neurosurgery 23:476–479 1988

9.

Chang CHHousepian EMHerbert C Jr: An operative staging system and megavoltage radiotherapeutic technique for cerebellar medulloblastoma. Radiology 93:135113631969Chang CH Housepian EM Herbert C Jr: An operative staging system and megavoltage radiotherapeutic technique for cerebellar medulloblastoma. Radiology 93:1351–1363 1969

10.

Duffner PKCohen MEMyers MHet al: Survival of children with brain tumors: SEER Program, 1973–1980. Neurology 36:5976011986Duffner PK Cohen ME Myers MH et al: Survival of children with brain tumors: SEER Program 1973–1980. Neurology 36:597–601 1986

11.

Finlay JL: Current status of the Childrens Cancer Study Group (CCSG) brain tumor trials. J Neurooncol 4:1081986 (Abstract)Finlay JL: Current status of the Childrens Cancer Study Group (CCSG) brain tumor trials. J Neurooncol 4:108 1986 (Abstract)

12.

Finlay JLGoins SCUteg Ret al: Progress in the management of childhood brain tumors. Hematol Oncol Clin North Am 1:7537761987Finlay JL Goins SC Uteg R et al: Progress in the management of childhood brain tumors. Hematol Oncol Clin North Am 1:753–776 1987

13.

Friedman HSMahaley MS JrSchold SC Jret al: Efficacy of vincristine and cyclophosphamide in the therapy of recurrent medulloblastoma. Neurosurgery 18:3353401986Friedman HS Mahaley MS Jr Schold SC Jr et al: Efficacy of vincristine and cyclophosphamide in the therapy of recurrent medulloblastoma. Neurosurgery 18: 335–340 1986

14.

Friedman HSOakes WJ: The chemotherapy of posterior fossa tumors in childhood. J Neurooncol 5:2172291987Friedman HS Oakes WJ: The chemotherapy of posterior fossa tumors in childhood. J Neurooncol 5:217–229 1987

15.

Friedman HSSchold SC JrMahaley MS Jret al: Phase II treatment of medulloblastoma and pineoblastoma with Melphalan: clinical therapy based on experimental models of human medulloblastoma. J Clin Oncol 7:9049111989Friedman HS Schold SC Jr Mahaley MS Jr et al: Phase II treatment of medulloblastoma and pineoblastoma with Melphalan: clinical therapy based on experimental models of human medulloblastoma. J Clin Oncol 7:904–911 1989

16.

Hughes ENShillito JSallan SEet al: Medulloblastoma at the Joint Center for Radiation Therapy between 1968–1984. The influence of radiation dose on the patterns of failure and survival. Cancer 61:199219981988Hughes EN Shillito J Sallan SE et al: Medulloblastoma at the Joint Center for Radiation Therapy between 1968–1984. The influence of radiation dose on the patterns of failure and survival. Cancer 61:1992–1998 1988

17.

Kaplan ELMeier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:4574811958Kaplan EL Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481 1958

18.

Kretschmar CSTarbell NJKupsky Wet al: Pre-irradiation chemotherapy for infants and children with medulloblastoma: a preliminary report. J Neurosurg 71:8208251989Kretschmar CS Tarbell NJ Kupsky W. et al: Pre-irradiation chemotherapy for infants and children with medulloblastoma: a preliminary report. J Neurosurg 71:820–825 1989

19.

Levin VARodriguez LAEdwards MSBet al: Treatment of medulloblastoma with procarbazine, hydroxyurea, and reduced radiation doses to whole brain and spine. J Neurosurg 68:3833871988Levin VA Rodriguez LA Edwards MSB et al: Treatment of medulloblastoma with procarbazine hydroxyurea and reduced radiation doses to whole brain and spine. J Neurosurg 68:383–387 1988

20.

Mantel N: Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50:1631701966Mantel N: Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50:163–170 1966

21.

McIntosh SChen MSartain PAet al: Adjuvant chemotherapy for medulloblastoma. Cancer 56:131613191985McIntosh S Chen M Sartain PA et al: Adjuvant chemotherapy for medulloblastoma. Cancer 56:1316–1319 1985

22.

Miller ABHoogstraten BStaquet Met al: Reporting results of cancer treatment. Cancer 47:2072141981Miller AB Hoogstraten B Staquet M et al: Reporting results of cancer treatment. Cancer 47:207–214 1981

23.

Neidhardt MKBailey CC: Prospective randomized co-operative medulloblastoma trial (MED 84) of the International Society of Paediatric Oncology (SIOP) and of the (German) Society of Paediatric Oncology (GPO). Childs Nerv Syst 3:70731987Neidhardt MK Bailey CC: Prospective randomized co-operative medulloblastoma trial (MED 84) of the International Society of Paediatric Oncology (SIOP) and of the (German) Society of Paediatric Oncology (GPO). Childs Nerv Syst 3:70–73 1987

24.

O'Brien PC: Comparing two samples: extensions of the t, Rank-Sum and Log-Rank Tests. J Am Stat Assoc 8:52611988O'Brien PC: Comparing two samples: extensions of the t Rank-Sum and Log-Rank Tests. J Am Stat Assoc 8: 52–61 1988

25.

Packer RJSiegel KRSutton LNet al: Efficacy of adjuvant chemotherapy for patients with poor-risk medulloblastoma: a preliminary report. Ann Neurol 24:5035081988Packer RJ Siegel KR Sutton LN et al: Efficacy of adjuvant chemotherapy for patients with poor-risk medulloblastoma: a preliminary report. Ann Neurol 24:503–508 1988

26.

Rivera-Luna RRueda-Franco FLanche-Guevara MTet al: Multidisciplinary treatment of medulloblastomas in childhood. Childs Nerv Syst 3:2282311987Rivera-Luna R Rueda-Franco F Lanche-Guevara MT et al: Multidisciplinary treatment of medulloblastomas in childhood. Childs Nerv Syst 3:228–231 1987

27.

Snedecor GWCochran WG: Statistical Methods. Ames, Iowa: Iowa State University Press1981 pp 228253Snedecor GW Cochran WG: Statistical Methods. Ames Iowa: Iowa State University Press 1981 pp 228–253

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