Surgery in Treating Children With Neuroblastoma

OBJECTIVES:

- To determine if asymptomatic patients with low-risk neuroblastoma treated with surgery
alone will have a 3-year survival rate of 95%.

- Estimate the response and 3-year event-free survival rates of symptomatic patients
treated with chemotherapy.

- Estimate the event-free survival and overall survival rates in patients who relapse or
progress after initial treatment with surgery alone.

- Determine the acute and chronic toxic effects associated with treating low-risk
neuroblastoma with surgery alone or surgery and chemotherapy.

OUTLINE: This is a multicenter study. Patients are stratified according to disease stage,
MYCN status, age, and histology.

Patients undergo primary tumor resection and biopsy of regional nodes. Patients with at
least 50% of the tumor resected are followed monthly for 3 months, every 3 months for 9
months, every 6 months for one year, and then annually thereafter.

Regimen I

- Patients with clinically symptomatic (e.g., respiratory distress, spinal cord
compromise with or without neurologic deficit, inferior vena cava compression with
renal or bowel ischemia, intractable vomiting due to gastrointestinal obstruction,
genitourinary obstruction, or coagulopathy) low-risk neuroblastoma or who have less
than 50% of the primary tumor resected receive 4 different courses of chemotherapy.

- Course 1: Patients receive carboplatin IV over 1 hour followed by etoposide IV over 2
hours on day 0 and etoposide only on days 1 and 2.

- Course 2: Patients receive carboplatin IV over 1 hour, cyclophosphamide IV over 1 hour,
and doxorubicin IV over 15-60 minutes on day 1.

- Course 3: Patients receive cyclophosphamide IV over 1 hour followed by etoposide IV
over 2 hours on day 0 and etoposide only on days 1 and 2.

- Course 4: Patients receive carboplatin IV over 1 hour and etoposide IV over 2 hours
followed by doxorubicin IV over 15-60 minutes on day 0 and etoposide only on days 1 and
2.

Regimen II

- Patients who progress to or recur with unfavorable biology intermediate-risk disease
receive an additional 4 courses of chemotherapy.

- Course 5: Patients receive treatment as in course 3 above.

- Course 6: Patients receive treatment as in course 2 above.

- Course 7: Patients receive treatment as in course 1 above.

- Course 8: Patients receive cyclophosphamide IV over 1 hour followed by doxorubicin IV
over 15-60 minutes on day 1.

All infants under 60 days of age receive filgrastim (G-CSF) or sargramostim (GM-CSF)
subcutaneously beginning 24 to 36 hours after chemotherapy and continuing until blood counts
recover.

Courses in both regimens repeat every 3 weeks in the absence of unacceptable toxicity.

Patients at risk for symptomatic spinal cord compression may also receive chemotherapy.
Patients experiencing progressive or recurrent disease after observation undergo repeat
surgery and/or chemotherapy as above. Patients with clinically symptomatic disease may also
undergo radiotherapy if response to chemotherapy is not rapid.

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

PROJECTED ACCRUAL: A total of 820 patients will be accrued for this study within 4 years.

DISEASE CHARACTERISTICS:

- Histologically proven low-risk neuroblastoma (excluding ganglioneuroma)

- International Neuroblastoma Staging System (INSS) stage 1 in all patients

- INSS stage 2A or 2B in patients less than 365 days of age

- INSS stage 2A or 2B tumor with nonamplified MYCN with any Shimada histology in
patients ages 1 to 20 years

- INSS stage 2A or 2B tumor with amplified MYCN with Shimada favorable histology
in patients ages 1 to 20 years

- INSS stage 4S tumors with nonamplified MYCN, Shimada favorable histology, and a
DNA index not equal to 1 in patients less than 365 days of age

- Immediate chemotherapy allowed prior to biopsy for patients with intradural extension
and/or emergent paresis if biopsy performed within 96 hours

- Must have no abnormal organ function unless due to neuroblastoma

- Concurrent registration on companion biology study (protocol COG-ANBL00B1) or its
successor

PATIENT CHARACTERISTICS:

Age:

- Under 21

Performance status:

- Not specified

Life expectancy:

- Not specified

Hematopoietic:

- Not specified

Hepatic:

- Bilirubin less than 1.5 times normal

- SGOT or SGPT less than 2.5 times normal

Renal:

- Creatinine less than 1.5 times normal

Cardiovascular:

- Shortening fraction greater than 27% by echocardiogram OR

- Ejection fraction greater than 47% by radionuclide angiogram

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No prior immunotherapy

Chemotherapy:

- See Disease Characteristics

Endocrine therapy:

- No prior hormonal therapy

Radiotherapy:

- No prior radiotherapy

Surgery:

- Prior surgery allowed

Other:

- No other prior therapy