Fenretinide in Treating Patients With Metastatic or Unresectable Malignant Solid Tumors

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed solid tumor malignancy

  • Metastatic and/or unresectable disease
• No standard curative or palliative measures exist or remain effective
• Measurable or evaluable disease
• No known brain metastases unless previously resected or irradiated with no treatment with steroids for more than 1 month

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
• Life expectancy > 3 months
• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 75,000/mm³
• Bilirubin < 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN (5 times ULN for patients with known liver metastases)
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception prior to, during, and for ≥ 6 months after completion of study treatment
• No uncontrolled diabetes mellitus at high risk for hypertriglyceridemia (i.e., fasting serum glucose concentration > 200 mg/dL OR hemoglobin A1C > 7.5%)
• No egg allergy
• No history of allergic reactions to compounds of similar chemical or biologic composition to fenretinide (e.g., isotretinoin, vitamin A, or tretinoin)

• No uncontrolled intercurrent illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would preclude compliance with study requirements
• No known hypertriglyceridemia requiring medication
• No identified familial hyperlipidemia disorder

PRIOR CONCURRENT THERAPY:

• Recovered from all prior therapy
• Prior treatment with oral fenretinide is allowed provided no severe toxicity occurred
• At least 2 weeks since prior major surgery

• More than 4 weeks since prior chemotherapy or radiotherapy

  • At least 6 weeks since prior nitrosoureas or mitomycin C
• No other concurrent investigational agents
• No other concurrent anticancer chemotherapy
• No other concurrent antioxidants*
• No concurrent hormone-ablative agents, including steroids, except for adrenal replacement or anti-inflammatory indications
• No other concurrent anticancer agents or therapies
• No concurrent herbal or other alternative therapies*

• No concurrent vitamin supplements (e.g., vitamin A, ascorbic acid, or vitamin E)*

  • Standard-dose multivitamin allowed

• No other concurrent medications that may act as modulators of intracellular ceramide levels or ceramide cytotoxicity, sphingolipid transport, p-glycoprotein, multidrug resistance protein 1 (MRP1), or MRP1 drug/lipid transporters, including any of the following*:

  • Cyclosporine or any of its analogues
  • Verapamil
  • Tamoxifen or its analogue
  • Ketoconazole
  • Chlorpromazine
  • Mifepristone
  • Indomethacin
  • Sulfinpyrazone NOTE: *Patients who have discontinued these drugs for ≥ 1 week are eligible

• No concurrent medications that may cause pseudotumor cerebri, including any of the following:

  • Tetracycline
  • Nalidixic acid
  • Nitrofurantoin
  • Phenytoin
  • Sulfonamides
  • Lithium
  • Amiodarone
• No concurrent total parenteral nutrition (TPN) with intralipids
• No concurrent combination antiretroviral therapy for HIV-positive patients