• Relapse-free survival [ Designated as safety issue: No ]
  
• Survival [ Designated as safety issue: No ]
  
• Exoprimary-site relapse rate [ Designated as safety issue: No ]
  
• Time to first recurrence [ Designated as safety issue: No ]
  
• Degree of neurocognitive post-treatment decline or dysfunction as measured by an IQ test at baseline and after 1, 2, and 3 years [ Designated as safety issue: No ]
  
• Degree of hearing loss [ Designated as safety issue: No ]
  
• Decline in growth, sexual maturation, or need for hormone replacement [ Designated as safety issue: No ]
  
• Adverse events [ Designated as safety issue: Yes ]
  

OBJECTIVES:

• Reduce the late cognitive, auditory, and endocrinologic effects in children with newly diagnosed standard-risk posterior fossa primitive neuroectodermal tumor or medulloblastoma by reducing the adjuvant craniospinal radiotherapy dose by 25%, but maintaining a therapeutic efficacy (86% 3-year relapse-free survival) of current standard therapy by using maintenance chemotherapy comprising lomustine, cisplatin, and vincristine alternated with cyclophosphamide and etoposide.
• Evaluate the acute and subacute toxicity of this regimen in these patients.
• Evaluate the late neurotoxic effects of low-dose craniospinal radiotherapy, in terms of cognitive, endocrinologic, and auditory function, in these patients.

OUTLINE: This is a multicenter study.

• Adjuvant induction chemoradiotherapy: Beginning within 28 days after prior resection, patients undergo radiotherapy to the craniospinal axis 5 days a week for 2 weeks and then conformal radiotherapy to the tumor bed 5 days a week for 4 weeks. Beginning 1 week after the initiation of radiotherapy, patients receive vincristine IV weekly for 6 weeks.

• Maintenance chemotherapy: Beginning 4 weeks after the completion of induction chemoradiotherapy, patients receive two 6-week courses of regimen A as outlined below alternated with one 6-week course of regimen B as outlined below for a total of 9 courses (6 courses of regimen A and 3 courses of regimen B).

  • Regimen A: Patients receive oral lomustine and cisplatin IV over 8 hours on day 0 and vincristine IV on days 0, 7, and 14.
  • Regimen B: Patients receive cyclophosphamide IV on days 0 and 1 and etoposide IV on days 0 and 1 and then orally on days 14-34.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 3 years.