Combination Chemotherapy in Treating Children With Neuroblastoma

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Combination chemotherapy plus surgery may be an effective treatment for neuroblastoma.

PURPOSE: This phase III trial is studying how well combination chemotherapy followed by surgery works in treating young patients with neuroblastoma.

OBJECTIVES:

* Determine whether the use of selected prognostic variables to assign treatment increases the event-free survival and overall survival in children with intermediate-risk neuroblastoma.
* Determine the acute and long-term morbidity and toxicity of surgery and combination chemotherapy in this patient population.
* Assess the relationship between extent of tumor resection and event-free and overall survival in patients treated with this regimen.

OUTLINE: Patients receive carboplatin IV over 1 hour on days 0, 21, and 63; cyclophosphamide IV over 1 hour on days 21 and 42; doxorubicin IV over 15-60 minutes on days 21 and 63; and etoposide IV over 2 hours on days 0-2, 42-44, and 63-65. Patients under 60 days of age also receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning 24 hours after the last chemotherapy administration and continuing until blood counts recover. Patients with favorable biology who do not achieve complete remission then undergo surgery to remove or debulk residual disease on day 84 or when blood counts recover. Patients with favorable biology who achieve partial response and surgery to the primary site is not deemed in the best interest of the patient may receive additional chemotherapy (as below) and delay surgery to the primary site after completion of chemotherapy.

Patients with unfavorable biology receive additional chemotherapy comprising cyclophosphamide IV over 1 hour on days 84, 105, and 147; etoposide IV over 2 hours on days 84-86 and 126-128; carboplatin IV over 1 hour on days 105 and 126; and doxorubicin IV over 15-60 minutes on days 105 and 147. Patients then undergo debulking surgery on day 168 or when blood counts recover.

Some patients may then undergo radiotherapy after surgery.

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

PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically proven neuroblastoma or maturing ganglioneuroma that is judged to be intermediate risk by one of the following criteria:

  * International Neuroblastoma Staging System (INSS) stage III

    * Under 1 year old, MYCN oncogene nonamplified, and any ploidy
    * 1 to 20 years old, MYCN nonamplified, favorable Shimada histology
  * INSS stage IV

    * Under 1 year old, MYCN nonamplified, any ploidy
  * INSS stage IVS

    * Under 1 year old, MYCN nonamplified, unfavorable Shimada histology and any ploidy OR favorable Shimada histology and diploidy
* All patients must be registered on the companion neuroblastoma biology study (COG-ANBL00B1)

PATIENT CHARACTERISTICS:

Age:

* Under 21

Performance status:

* Not specified

Life expectancy:

* Not specified

Hematopoietic:

* Not specified

Hepatic:

* Not specified

Renal:

* Not specified

Other:

* No abnormal organ function that would prohibit chemotherapy unless due to neuroblastoma

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* Prior chemotherapy for patients with intradural extension and emergent paresis allowed provided biopsy was performed within 96 hours after treatment

Endocrine therapy:

* Not specified

Radiotherapy:

* Not specified

Surgery:

* Not specified

Other:

* No other prior therapy