Combination Chemotherapy With or Without Radiation Therapy in Treating Children With Brain Tumors

Management of Children Aged Less Than 3 Years With Brain Tumors

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy after chemotherapy may kill any remaining tumor cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with or without radiation therapy works in treating children with brain tumors.

OBJECTIVES:

• Determine the response rate in children under 36 months of age with primary brain or brain stem tumors treated with vincristine, methotrexate, carboplatin, cyclophosphamide, and cisplatin with or without radiotherapy.
• Determine the event-free survival and overall survival in children treated with this regimen.
• Determine the pattern of local recurrence or occurrence of CNS metastases in children treated with this regimen.
• Determine the quality of life in children treated with this regimen.
• Determine the tolerability and long-term toxicity of this regimen in these children.
• Determine the proportion of children who require radiotherapy after treatment with this regimen.
• Determine the prognosis of children who receive both chemotherapy and radiotherapy.
• Determine the nature and behavior of brain tumors in very young children.

OUTLINE: This is a multicenter study.

• Chemotherapy: Patients receive vincristine IV on days 0, 14, and 28; carboplatin IV over 4 hours on day 0; methotrexate IV continuously over 24 hours on day 14; cyclophosphamide IV over 4 hours on day 28; and cisplatin IV continuously over 48 hours on days 42 and 43. Courses repeat every 56 days (8 weeks) for up to 12 months. Patients who achieve a complete response proceed to observation, as do those achieving a partial response with no tumor present on biopsy. Patients with biopsy proven residual tumors after 12 months of chemotherapy or recurrent tumors that don't have the potential to spread through the cerebrospinal fluid (CSF) proceed to local radiotherapy. Patients with unresponsive disease or progressive disease that has the potential to spread through the CSF proceed to craniospinal radiotherapy.
• Local radiotherapy: Patients undergo local radiotherapy 5 days a week for 5-5½ weeks.
• Craniospinal radiotherapy: Patients undergo craniospinal radiotherapy 5 days a week for 4 weeks.

Quality of life is assessed periodically.

After completion of study treatment, patients are followed periodically for at least 2 years.

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

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

  • Brain stem tumor (histological confirmation not required)

  • Histologically confirmed primary intracranial brain tumor of 1 of the following histologies:

    • Anaplastic (malignant) astrocytoma
    • Glioblastoma
    • Anaplastic (malignant) oligodendroglioma
    • Ependymoma
    • Anaplastic (malignant) ependymoma
    • Anaplastic (malignant) oligoastrocytoma
    • Choroid plexus carcinoma
    • Astroblastoma
    • Polar spongioblastoma
    • Gliomatosis cerebri
    • Anaplastic (malignant) ganglioglioma
    • Pineoblastoma
    • Mixed pineocytoma or pineoblastoma
    • Medulloepithelioma
    • Neuroblastoma
    • Ependymoblastoma
    • Primitive neuroectodermal tumors (PNETs), including medulloblastoma or cerebral or spinal PNETs

• Has undergone surgery or biopsy of the tumor within the past 2-4 weeks

PATIENT CHARACTERISTICS:

• No concurrent unrelated disease, including hematological or renal disease, that would preclude study treatment

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or radiotherapy

• Prior steroids allowed

• No concurrent steroids as anti-emetics

  • Concurrent steroids allowed for control of tumor-related symptoms