PRIMARY OBJECTIVES: I. To assess the PSA response in prostate cancer patients with only biochemical recurrence after local curative therapy who are then treated with fenretinide (4-HPR). II. To assess PSA doubling time as a measure of disease activity, time to PSA progression in prostate cancer patients receiving fenretinide. III. To evaluate the qualitative and quantitative toxicities of this agent in this patient population. IV. To evaluate pharmacokinetic studies on the bioavailability of 4-HPR in this patient population. OUTLINE: This is a multicenter study. Patients are stratified according to prior therapy (surgery vs radiotherapy and/or brachytherapy vs both), stage at diagnosis (organ confined vs extra-capsular extension vs lymph node positive), Gleason score at diagnosis (2-4 vs 5-6 vs 7-10), and prostate-specific antigen level at diagnosis (0-4 ng/mL vs 4.1-10 ng/mL vs > 10 ng/mL). Patients receive oral fenretinide twice daily on days 1-7. Courses repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
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 \< 4 ng/mL for patients treated with primary radiation and \< 0.3 ng/mL for patients treated with radical prostatectomy, with no clinical or radiographic evidence of metastatic disease; the rising PSA must be confirmed by two consecutive increases, separated by at least 2 weeks; the absolute PSA value must be \> 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 \< 4ng/mL * Bone scan negative for metastatic disease within 4 weeks prior to registration * Patients must have a performance status of 0, 1, or 2 * The effects of fenretinide on fetal conception and development at the recommended therapeutic dose are unknown; for this reason, men enrolled in this trial must agree to use adequate contraception prior to study entry and for the duration of study participation * Peripheral absolute neutrophil count (ANC) \>= 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 =\< 1.5 gm/dL * Creatinine clearance or radioisotope GFR \>= 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 A or analogue; verapamil; tamoxifen or analogue; ketoconazole, chlorpromazine; RU486; indomethacin; or sulfinpyrazone * Patients with known uncontrolled hypertriglyceridemia resulting in pancreatitis are excluded from study; patients with fasting triglycerides equal to or greater then 300mg/dl should start on medical treatment for hypertriglyceridemia (ex. fibrate derivatives); fenretinide will only be started when triglycerides are less than 300mg/dl * Patients with known retinopathy from any source are excluded from the protocol as elevated ceramide levels from Fenretinide may exacerbate and/or lead to permanent retinal damage in this population * Patients taking antioxidant supplements (vitamin C or E) must discontinue use before being eligible for protocol
is designated in this study