Combination Chemotherapy and Radiation Therapy in Treating Patients With Germ Cell Tumors in the Brain

OBJECTIVES:

Primary

• Evaluate and compare, in a non-randomized protocol, reduced-dose craniospinal radiotherapy alone or combination chemotherapy comprising carboplatin, etoposide phosphate, and ifosfamide and local irradiation in patients with intracranial germinoma.
• Increase survival with combination chemotherapy comprising cisplatin, etoposide phosphate, and ifosfamide followed by focal radiotherapy or craniospinal irradiation in patients with intracranial secreting germ cell tumors.

Secondary

• Use the same diagnostic protocol for imaging and laboratory investigations before, during, and after treatment.
• Establish and use a common documentation system regarding general patient's data, including diagnostic tests, clinical evaluation, surgery, histology, radiotherapy, chemotherapy, and toxicity.
• Collect information about toxicity, prognostic factors, and tumor markers.
• Collect epidemiological data, including documentation of incidence and the site and the histologic pattern of intracranial secreting and nonsecreting germ cell tumors in children and adolescents.
• Register associated malformations in the patients as well as the epidemiology of tumors and malformations in relatives.

OUTLINE: This is a non-randomized, multicenter study. Patients are stratified according to tumor classification (pure CNS germinoma vs secreting germ cell tumor and embryonal carcinoma).

Patients in stratum I undergo biopsy or surgical resection and then begin radiotherapy with or without chemotherapy.

• Stratum I (pure CNS germinoma [without elevated markers]): Patients receive 1 of 2 treatment options based on national/center standard:

• Option 1: Patients receive reduced-dose craniospinal radiotherapy 5 days a week for 3 weeks followed by a boost to the tumor bed 5 days a week for 2 weeks. Patients with multifocal or metastatic disease receive additional boosts to the tumor sites.
• Option 2: Patients receive carboplatin IV over 1 hour on day 1, etoposide phosphate IV over 1 hour on days 1-3 and 22-24, and ifosfamide IV over 3 hours on days 22-26. Treatment repeats every 6 weeks for 2 courses. After recovery from chemotherapy, patients undergo radiotherapy 5 days a week for 5 weeks.
• Stratum II (secreting tumors and embryonal carcinoma): Patients receive etoposide phosphate IV over 1 hour on days 1-3, cisplatin IV over 1 hour on days 1-5, and ifosfamide IV over 22 hours on days 1-5. Treatment repeats every 3 weeks for up to 4 courses. Patients whose tumor markers do not return to normal after completion of chemotherapy are off protocol. Patients may undergo surgery after chemotherapy course 2 or 4 if required. After completion of chemotherapy and recovery from surgery, patients with nonmetastatic disease undergo radiotherapy to the tumor bed 5 day a week for 6 weeks, and patients with metastatic disease undergo radiotherapy to the cerebrum, spinal axis, and tumor bed for 7 weeks.

After completion of study treatment, patients are followed for 4 weeks and then periodically.

PROJECTED ACCRUAL: Approximately 500 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Clinical and radiological evidence of intracranial germ cell tumor, classified as 1 of the following:

• Germinoma

• Pure germinoma
• Germinoma with mature and/or immature teratoma
• Secreting germ cell tumor

• Elevated tumor markers in serum and/or cerebral spinal fluid as evidenced by any of the following:

• Alpha-fetoprotein > 25 ng/mL
• β-human choriogonadotropin > 50 IU/L
• Any tumor containing 1 of these components:

• Yolk sac tumor
• Choriocarcinoma
• Embryonal tumor

• Normal tumor markers allowed
• Diagnosis confirmed by histology or elevated serum markers
• Metastatic or nonmetastatic disease

• Two separate tumors in the suprasellar and pineal areas without evidence of metastatic disease elsewhere are considered nonmetastatic multifocal disease
• Study treatment must begin ≤ 4 weeks after diagnosis
• No pure immature or mature teratomas
• The following additional patients are eligible:

• Patients who are > 18 years of age provided no other appropriate protocol exists
• Patients who were diagnosed > 4 weeks ago
• Patients who are in relapse

PATIENT CHARACTERISTICS:

• Not specified

PRIOR CONCURRENT THERAPY:

• No prior treatment except surgery
• No concurrent amino glycosides or other nephrotoxic drugs during ifosfamide administration
• No concurrent growth factors
• No other concurrent chemotherapy or radiotherapy