Phenelzine Sulfate and Docetaxel in Treating Patients With Prostate Cancer With Progressive Disease After First-Line Therapy With Docetaxel

Inclusion Criteria:

* Histological or cytological diagnosis of adenocarcinoma of the prostate
* Radiographic evidence of regional or distant metastases with suspected tumor in an area that is safe to biopsy
* Willingness to undergo tumor biopsy
* Evidence of CRPC indicated by history of progression despite standard hormonal therapy (by PSA and/or imaging studies)
* Planned or recent initiation of standard docetaxel therapy; patients may be enrolled after receiving standard docetaxel therapy as long as the patient has not demonstrated evidence of progression for more than 45 days before enrollment ("late enrollers")
* For patients who have been on anti-androgen therapy and had evidence of response to the addition of an anti-androgen (i.e., PSA reduction), patients must have discontinued anti-androgen therapy for at least six weeks (4 weeks for flutamide) without current evidence of an anti-androgen withdrawal response
* Serum testosterone levels \< 50 ng/dL (unless surgically castrate); patients must continue androgen deprivation with an luteinizing hormone releasing hormone (LHRH) agonist if they have not undergone orchiectomy
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
* Has recovered from all therapy-related toxicity to =\< grade 2 (except alopecia, anemia and any signs or symptoms of androgen deprivation therapy)
* Absolute neutrophil count \>= 1500/uL
* Platelets \>= 100,000
* Creatinine =\< 1.5 times upper limit of normal (ULN)
* Bilirubin =\< 1.5 times ULN (if total bilirubin elevated, but direct is within normal limits \[WNL\], patient is eligible)
* Alanine aminotransferase (ALT) =\< 2.5 times ULN
* PSA \> 2 ng/mL (at the time of enrollment or prior to initiation of docetaxel)
* Life expectancy \> 3 months
* Signed informed consent

Exclusion Criteria:

* Significant peripheral neuropathy defined as grade 2 or higher
* A second active malignancy except adequately treated non-melanoma skin cancer or other non-invasive or in situ neoplasm
* Significant active concurrent medical illness or infection precluding protocol treatment or survival
* Current uncontrolled hyperthyroidism
* Pheochromocytoma
* Carcinoid Syndrome
* Known or suspected brain metastases
* Treatment with radiotherapy within the past 4 weeks or radiopharmaceutical therapy (strontium, samarium) within the past 8 weeks
* Concurrent therapy with a Selective Serotonin Reuptake Inhibitor (SSRI), tricyclic antidepressant, or Monoamine Oxidase Inhibitor (MAOi); clinical judgment should be used in a decision to discontinue antidepressants; a minimum of a 1 week washout period is required for any tricyclic or related antidepressant, or any SSRI (2 weeks for paroxetine or sertraline, 5 weeks for fluoxetine); minimum 2 week washout for any MAOi
* Concurrent therapy with any excluded medications that cannot be safely discontinued prior to initiation of combination therapy; discontinuation prior to enrollment is not required, but discontinuation prior to combination therapy must be possible
* Caution should be exercised in patients who are regularly taking narcotic analgesics, particularly higher doses; the doses of narcotic analgesics may need to be reduced, patients may need to be monitored closely for drug interactions, and the risks and benefits of participation in the study should be considered; clinical judgment should be exercised to manage this potential drug interaction