Neoadjuvant Chemotherapy With or Without Second-Look Surgery Followed by Radiation Therapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Intracranial Germ Cell Tumors

OBJECTIVES:

- Determine the response rate of patients with non-germinomatous germ cell tumors treated
with neoadjuvant chemotherapy.

- Determine the progression-free survival and overall survival of patients treated with
neoadjuvant chemotherapy with or without second-look surgery followed by radiotherapy
with or without autologous peripheral blood stem cell transplantation (PBSCT).

- Determine whether additional complete responses can be achieved after high-dose thiotepa
and etoposide with PBSCT in patients with persistently positive markers, histological
evidence of residual malignant elements, or unresectable residual tumors after initial
neoadjuvant chemotherapy.

- Determine patterns of recurrence in patients treated with this regimen.

- Correlate tumor marker response with radiographic and clinical measures of response, as
well as findings at second-look surgery in patients with radiological evidence of
residual disease.

OUTLINE:

- Induction chemotherapy:

- Courses 1, 3, and 5: Patients receive carboplatin IV over 1 hour on day 1 and
etoposide IV over 1 hour on days 1-3. Beginning on day 4, patients receive
filgrastim (G-CSF) IV or subcutaneously (SC) for 10 days or until blood counts
recover. Courses are 3 weeks in duration.

- Courses 2, 4, and 6: Patients receive etoposide IV over 1 hour followed by
ifosfamide IV over 1 hour on days 1-5. Beginning on day 6, patients receive G-CSF
IV or SC for 10 days or until blood counts recover. Courses are 3 weeks in
duration.

Patients undergo re-evaluation. Patients with a complete response (CR) go directly to
radiotherapy. Approximately 3 weeks after completion of induction chemotherapy, all patients
with less than a CR are encouraged to undergo second-look surgery.

After second-look surgery, patients with a CR or a partial response (PR) go directly to
radiotherapy. Patients with less than a PR undergo consolidation chemotherapy with peripheral
blood stem cell rescue (PBSC) followed by radiotherapy.

- Consolidation chemotherapy: Patients undergo PBSC collection. Patients receive G-CSF SC
until PBSC collection is complete. Patients then receive thiotepa IV over 3 hours
followed by etoposide IV over 3 hours on days -5 to -3. PBSCs are reinfused on day 0.
Beginning on day 1 and continuing until blood counts recover, patients receive G-CSF SC
daily.

- Radiotherapy: All patients receive radiotherapy once daily 5 days a week for 5-6 weeks
beginning after recovery from induction chemotherapy or second-look surgery or within 9
weeks after PBSC reinfusion.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months
for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 80-100 patients will be accrued for this study within 36-42
months.

DISEASE CHARACTERISTICS:

- One of the following diagnoses:

- Histologically confirmed intracranial non-germinomatous germ cell tumor (NGGCT)
of 1 of the following types:

- Endodermal sinus tumor (yolk sac tumor)

- Embryonal carcinoma

- Choriocarcinoma

- Immature teratoma and teratoma with malignant transformation

- Mixed germ cell tumor

- Histologically confirmed germinoma with elevation of serum/CSF beta human
chorionic gonadotropin (HCG) levels greater than 50 mIU/mL or any serum/CSF
alpha-fetoprotein (AFP) levels greater than 10 ng/ml or above institutional norm

- Histologically unconfirmed pineal and/or suprasellar tumors with serum/CSF beta
HCG levels greater than 50 mIU/mL or AFP levels greater than 10 ng/ml or above
institutional norm

- Patients with normal AFP and beta HCG < 50 mIU/mL without histologic diagnosis of a
NGGCT or patients with pure germinoma without elevation of tumor marker are ineligible

- Initial diagnosis within the past 31 days

PATIENT CHARACTERISTICS:

Age

- 3 to 24 at diagnosis

Performance status

- No minimum performance level

Life expectancy

- At least 8 weeks

Hematopoietic

- Absolute neutrophil count at least 1,000/mm^3

- Platelet count at least 100,000/mm^3 (transfusion independent)

- Hemoglobin at least 10.0 g/dL (transfusion allowed)

Hepatic

- Bilirubin no greater than 1.5 times upper limit of normal (ULN)

- ALT no greater than 2.5 times ULN

Renal

- Creatinine no greater than 1.5 times ULN OR

- Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

Pulmonary

- No assisted ventilation

Other

- Seizure disorders allowed

- No patients in status or coma

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patient must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- Not specified

Endocrine therapy

- Prior corticosteroids allowed

- Concurrent corticosteroids allowed

- Concurrent endocrine replacement therapy allowed (e.g., L-thyroxine, testosterone,
estrogen, desmopressin acetate)

- No concurrent growth hormone therapy

Radiotherapy

- Not specified

Surgery

- More than 1 prior surgery allowed

Other

- No other prior therapy for malignancy