DISEASE CHARACTERISTICS:
Diagnosis of neuroblastoma either by histological confirmation and/or demonstration of
tumor cells in the bone marrow with increased urinary catecholamines
Differentiating ganglioneuroblastoma allowed
No histological evidence only of ganglioneuroma by tumor biopsy or bone
marrow biopsy
High-risk disease meeting at least one of the following criteria:
Recurrent/progressive disease at any time
Refractory disease (i.e. less than a partial response to front-line therapy that
included ? 4 courses of chemotherapy)
Persistent disease after at least a partial response to front-line therapy (i.e.
still has residual disease by MIBG CT/MRI or bone marrow biopsy)
Biopsy of at least one residual site demonstrating viable neuroblastoma
required (tumor by bone marrow morphology is considered adequate
documentation of disease)
Measurable disease meeting at least one of the following criteria:
Measurable tumor on MRI or CT scan defined as at least one unidimensionally
measurable lesion ? 20 mm by conventional techniques or ? 10 mm by spiral CT
scan
For patients with persistent disease a biopsy* of bone marrow or bone or
soft tissue site must have demonstrated viable neuroblastoma
MIBG scan with positive uptake at a minimum of one site
For patients with persistent disease a biopsy* of a MIBG positive site must
have demonstrated viable neuroblastoma
Bone marrow with tumor cells seen on routine morphology (not by NSE staining
only) of bilateral aspirate and/or biopsy of one bone marrow sample NOTE: *If the
lesion was irradiated the biopsy must have been done at least 4 weeks after
completion of radiotherapy
No CNS parenchymal or meningeal-based lesions
Skull-based tumor lesions with or without intracranial extension are allowed
provided there are no neurologic signs or symptoms or hydrocephalus related to
the lesion
Patients with a history of complete surgical resection of CNS lesions are
eligible provided there is no evidence of CNS lesions by MRI or CT scan at study
entry
Patients with a history of CNS lesions must be off corticosteroid therapy for CNS
lesions for ? 4 weeks
PATIENT CHARACTERISTICS:
Performance status 0-2
Life expectancy ? 2 months
ANC ? 500/mm?
Platelet count ? 50 000/mm? (transfusion independent)
Hemoglobin ? 8.0 g/dL (transfusion independent)
Serum creatinine ? 1.5 times normal for age
Total bilirubin ? 1.5 times normal for age
ALT and AST ? 3 times normal for age
Serum triglycerides < 300 mg/dL
Serum calcium < 11.6 mg/dL
Lipase normal for age
PT/PTT ? 1.5 times upper limit of normal for age (without fresh frozen plasma support;
vitamin K allowed)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception prior to during and for 2 months
after completion of study treatment
LVEF ? 55% by ECHO or MUGA scan OR fractional shortening ? 27% by ECHO
No EKG abnormality
No dyspnea at rest exercise intolerance or requirement for oxygen
No hematuria and/or proteinuria > 1+ on urinalysis
No known history of allergy to egg products
No known history of allergy to soy bean oil
No skin toxicity > grade 1 per CTCAE v3
Seizure disorder allowed if seizures are controlled on anticonvulsants and the
anticonvulsant(s) is not contraindicated
Known genetic metabolic or psychiatric conditions or other ongoing serious medical
issues must be approved by the study chair prior to study registration
PRIOR CONCURRENT THERAPY:
Recovered from all prior chemotherapy immunotherapy or radiotherapy
More than 3 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas)
and/or biologic therapy without stem cell support
More than 7 days since prior hematopoietic growth factors
No prior radiotherapy to the only site of measurable disease unless there has been
subsequent disease progression at that site or a biopsy of that site showed viable
neuroblastoma ? 4 weeks after completion of radiotherapy
Prior CNS irradiation allowed
At least 2 weeks since prior small field (focal) radiotherapy
At least 6 weeks since prior large field radiotherapy (i.e. total-body irradiation
craniospinal radiotherapy whole abdominal or total lung radiotherapy or radiotherapy
to > 50% of marrow space)
At least 56 days since prior myeloablative autologous stem cell transplantation
At least 4 weeks since prior myelosuppressive therapy with stem cell support
At least 6 weeks since prior MIBG therapy
Prior oral fenretinide therapy allowed
At least 3 weeks since prior retinoid therapies
No prior organ transplantation
No prior myeloablative allogeneic stem cell transplantation unless stem cells were
from an identical twin sibling
No concurrent systemic corticosteroids including corticosteroids for emesis control
Concurrent inhaled corticosteroids for asthma control or steroids for metabolic
deficiency states allowed
Concurrent palliative radiotherapy allowed provided the irradiated sites will not be
used to measure response
No concurrent parenteral intralipids
No other concurrent chemotherapy or immunomodulating agents
No concurrent drugs suspected of causing pseudotumor cerebri including tetracycline
nalidixic acid nitrofurantoin phenytoin sulfonamides lithium or amiodarone
No concurrent vitamin A C or E supplements (except as part of routine total
parenteral nutrition [TPN] supplements or as part of a single daily standard dose of
oral multivitamin supplement)
No concurrent medications that may potentially act as modulators of intracellular
ceramide levels or ceramide cytotoxicity sphingolipid transport or p-glycoprotein
(MDR1) or MDR1 drug/lipid transporters including cyclosporine or analogue verapamil
tamoxifen or analogue ketoconazole chlorpromazine mifepristone (RU486)
indomethacin or sulfinpyrazone
No other concurrent anticancer agents
No concurrent herbal supplements or other alternative therapy medications
No concurrent anti-arrhythmia or inotropic cardiac medications
