RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying how well fenretinide works in treating children with recurrent or resistant neuroblastoma.

OBJECTIVES:

• Determine the response rate in pediatric patients with recurrent or resistant high-risk neuroblastoma treated with fenretinide.
• Determine the toxic effects of this drug in these patients.
• Determine the proportion of patients with disease detected only by bone marrow immunocytology, who clear all evidence of disease during treatment with this drug.
• Determine minimal residual disease response by marrow and meta-iodobenzylguanidine (MIBG) I 123 scan in patients treated with this drug.

OUTLINE: Patients are stratified according to presence of measurable disease on CT scan/MRI (yes vs no). A third stratum of patients with tumor cells in bone marrow by immunocytology only is enrolled but is not evaluated for response.

Patients receive oral fenretinide 3 times daily (or 2 times daily if over 18 years of age) on days 1-7. Treatment repeats every 3 weeks for up to 30 courses in the absence of disease progression or unacceptable toxicity. Patients in stratum III who fail to acheive a complete response after 8 courses of therapy are removed from study.

Patients are followed monthly until blood counts and visual acuity are stable or normalized and then every 6 months for 2 years and annually for 3 years.

PROJECTED ACCRUAL: A total of 70 patients (25 each for strata I and II, 20 for stratum III) will be accrued for this study within 1-2 years.

DISEASE CHARACTERISTICS:

• Diagnosis of recurrent or resistant/refractory high-risk neuroblastoma by one or both of the following:

  • Histological confirmation
  • Demonstration of tumor cells in bone marrow with increased urinary catecholamines

• Stratum I:

  • At least 1 unidimensionally measurable lesion*

    • At least 20 mm by MRI and/or CT scan OR at least 10 mm by spiral CT scan NOTE: *Previously irradiated lesions are not considered target lesions unless there is clear progression at the site after radiotherapy or a biopsy performed at least 4 weeks after completion of radiotherapy shows a viable neuroblastoma

• Stratum II: Meets one or both of the following criteria:

  • At least 1 site with positive uptake on meta-iodobenzylguanidine (MIBG) I 123 scan
  • Tumor in bilateral bone marrow aspirate/biopsy by routine morphology (no NSE staining only)

• Stratum III:

  • At least 5 tumor cells/10^6 mononuclear cells in the bone marrow by immunocytology only (on 2 successive bone marrows performed from 1 day to 4 weeks apart)
• Patients in first response (i.e., patients with persistent tumor at end of frontline therapy, but who have never had disease relapse or progression) must have histological* or morphological (by bone marrow) confirmation** of viable tumor on CT scan, MRI, or MIBG scan after completion of myeloablative therapy (for strata I and II) NOTE: *Histological confirmation waived for patients with a prior relapse (for strata I and II)

NOTE: **If lesion was irradiated, biopsy must be performed at least 4 weeks after completion of radiotherapy (for strata I and II)

• No catecholamine elevation only

PATIENT CHARACTERISTICS:

Age

• 21 and under at original diagnosis

Performance status

• 0-2

Life expectancy

• At least 2 months

Hematopoietic

• Hemoglobin greater than 7.5 g/dL (transfusion allowed)

Hepatic

• Bilirubin no greater than 1.5 times normal
• SGPT and SGOT less than 2.5 times normal

Renal

• Creatinine normal for age
• No hematuria or proteinuria greater than 1+ on urinalysis
• Calcium less than 11.6 mg/dL

Other

• Triglycerides less than 300 mg/dL
• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• No seizure disorders unless on anticonvulsants and well controlled
• No skin toxicity greater than grade 1
• Must be able to consume entire intact study capsule in the dosage prescribed for body surface area

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Recovered from prior immunotherapy
• At least 7 days since prior anticancer biologic therapy
• At least 2 days since prior growth factors
• Prior autologous stem cell transplantation allowed
• No prior allogeneic stem cell transplantation
• No concurrent immunomodulating agents

Chemotherapy

• At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
• No concurrent anticancer chemotherapy

Endocrine therapy

• No concurrent steroids

Radiotherapy

• See Disease Characteristics
• Recovered from prior radiotherapy
• At least 4 weeks since prior radiotherapy to target lesion
• Prior radiotherapy to nontarget lesions allowed
• No concurrent radiotherapy to sole measurable lesion for symptom relief
• Concurrent palliative radiotherapy to nontarget or localized painful lesions allowed

Surgery

• Not specified

Other

• Prior tretinoin or isotretinoin allowed
• At least 2 weeks since other prior retinoids
• No prior fenretinide
• No concurrent supplemental oral or IV vitamin A, ascorbic acid, or vitamin E (except if contained in routine total parenteral nutrition [TPN] vitamin supplements)
• No concurrent drugs suspected of causing pseudotumor cerebri (e.g., tetracycline, nalidixic acid, nitrofurantoin, phenytoin, sulfonamides, lithium, amiodarone, or vitamin A [except as part of routine TPN supplements])
• No other concurrent anticancer agents