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 \< 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