Fenretinide in Treating Children With Recurrent or Resistant Neuroblastoma

Inclusion Criteria:

• 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

• 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)
• No catecholamine elevation only
• Performance status - 0-2
• At least 2 months
• Hemoglobin greater than 7.5 g/dL (transfusion allowed)
• Bilirubin no greater than 1.5 times normal
• SGPT and SGOT less than 2.5 times normal
• Creatinine normal for age
• No hematuria or proteinuria greater than 1+ on urinalysis
• Calcium less than 11.6 mg/dL
• 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
• 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
• At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
• No concurrent anticancer chemotherapy
• No concurrent steroids
• Recovered from prior radiotherapy
• At least 4 weeks since prior radiotherapy to target lesion
• Prior radiotherapy to non target lesions allowed
• No concurrent radiotherapy to sole measurable lesion for symptom relief
• Concurrent palliative radiotherapy to non target or localized painful lesions allowed
• 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