Fenretinide in Treating Patients With Biochemically Recurrent Hormone-Naïve Prostate Cancer

Inclusion Criteria

• Patient must have a histologically or cytologically confirmed history of adenocarcinoma of the prostate
• Patients must have a rising PSA, following a nadir value of 2.0 ng/mL, and the increment of increase must be at least 0.5 ng/mL above the nadir
• Following radical prostatectomy, patients can have received adjuvant radiation therapy for positive margins or pT3 disease; patients may also have received radiation therapy for local recurrence, provided that they subsequently have a rising PSA after a new PSA nadir of = 1000/μL
• Platelet count >= 100, 000/μL (transfusion independent; defined as: without transfusion for 3 weeks prior to obtaining study entry value)
• Hemoglobin >= 8.0 gm/dL (may receive RBC transfusions or exogenous erythropoietin)
• Life expectancy of greater than 3 months
• Serum creatinine = = 50 ml/min/m2
• Total bilirubin =< 1.5 mg/dL
• SGOT (AST) and SGPT (ALT) < 2.5 x normal
• Patients with seizure disorders may be enrolled if on anticonvulsants and well controlled
• CNS toxicity =< Grade 2
• Patient must be able to consume the entire intact capsule(s) in the dosage prescribed for body surface area
• Triglycerides are less than 300mg/dl
• All patients will have malignancy confirmed by review of their biopsy specimens by the Division of Pathology of the City of Hope National Medical Center, the University of Southern California/LA County/Norris Comprehensive Cancer Center, or the University of California at Davis
• In patients who received radiotherapy, the absolute increase of PSA must be at least 2ng/ml to account for the "bounce" phenomenon

Exclusion Criteria

• Patients with evidence of metastatic disease
• PSA progression not verified by sequential rising PSA as discussed in Eligibility section
• Inability to take oral fenretinide
• Patients who have had prior cytotoxic chemotherapy or androgen ablative therapy
• Patients with history of receiving, or current administration of, chemotherapeutic agents, biological response modifiers, or corticosteroids; patients are permitted to have received up to 9 months of neoadjuvant or adjuvant hormone ablation in conjunction with their primary definitive therapy; androgen deprivation must have been completed at least one year prior to registration; no complementary or alternative therapy (e.g. St. John's Wort, PC-SPES, or other herbal remedies taken for the purpose of treating prostate cancer) may be given during protocol treatment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to fenretinide (i.e. retinoids)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/ social situations that would limit compliance with study requirements
• No prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ carcinoma of any site, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years
• Patients should not take any drugs suspected of causing pseudotumor cerebri, which include tetracycline, nalidixic acid, nitrofurantoin, phenytoin, sulfonamides, lithium, amiodarone, or vitamin A
• Patients may have received one prior investigational anti-cancer agent
• HIV-positive patients receiving combination anti-retroviral therapy are excluded from this study because of possible pharmacokinetic interactions with fenretinide; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated
• Patients should not concurrently take medications that may potentially act as modulators of intracellular ceramide levels or ceramide cytotoxicity, sphingolipid transport, or p-glycoprotein (MDR1) or MRP1 drug/lipid transporters, such as: cyclosporine