Oxaliplatin and Pemetrexed Disodium in Treating Patients With Refractory Hormone-Resistant Prostate Cancer

Inclusion Criteria:

* Histologically confirmed prostate cancer
* Measurable disease on computed tomography (CT) or evaluable disease on bone scan with an elevated PSA
* For patients who did not initially present with metastatic disease, definitive treatment with either radical prostatectomy or external beam radiation is permitted
* Documented progression on (a) two prior hormone treatments AND (b) one or two chemotherapy regimens
* Documented progression on two prior hormone therapies is defined as orchiectomy followed by anti-adrenal medication upon progression OR gonadotropin-releasing hormone (GnRH) analog +/- androgen receptor blocker with addition or subtraction upon progression; castrate level of testosterone must be documented at study entry
* Documented progression on taxane-based chemotherapy; in addition, patients may have failed a second prior chemotherapy regimen
* Palliative radiation therapy for metastatic disease is allowed only if less than 25% of total body bone marrow was irradiated; 28 days must have elapsed since completion of radiation therapy (RT) with bone marrow recovery; soft tissue disease irradiated in the prior 2 months may not be designated as measurable disease
* ECOG performance score of 0-2
* Absolute neutrophil count (ANC) \>= 1500/uL
* Platelet count \>= 100,000/uL
* Creatinine clearance \>= 45 mL/min
* Serum total bilirubin =\<1.5 mg/dL
* Alkaline phosphatase =\< 3x the upper limit of normal (ULN) for the reference lab (=\< 5x the ULN for patients with known hepatic metastases) and no upper limit for patients with known bone metastases
* Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT) =\< 3x the ULN for the reference lab (=\< 5x the ULN for patients with known hepatic metastases)
* Patients must be recovered from both acute and late effects of any prior surgery, radiotherapy or other antineoplastic therapy
* Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial
* Men of childbearing potential must consent to use barrier contraception while on treatment and for 90 days thereafter
* Patients with pleural or peritoneal effusions are eligible
* Willingness and ability to take vitamin supplementation and steroid premedication as specified in protocol
* Patients with superficial bladder cancer or skin cancer who have second malignancy within 5 years which was removed with curative intent

Exclusion Criteria:

* Active infection or with a fever \>= 38.5 degrees Celsius (C) within 3 days of the first scheduled protocol treatment
* Patients with brain metastases
* Prior malignancy within the past 5 years, except for curatively treated basal cell or squamous cell carcinoma of the skin or superficial bladder cancer
* Known hypersensitivity to any of the components of oxaliplatin or pemetrexed
* Received radiotherapy to more than 25% of their bone marrow, or patients who received any radiotherapy within 4 weeks of entry
* Received treatment with strontium
* Receiving concurrent investigational therapy or who have received investigational therapy within 30 days of the first scheduled day of protocol treatment
* Life expectancy \< 6 months
* Peripheral neuropathy \>= Grade 2
* Any other medical condition, including mental illness or substance abuse
* History of allogeneic transplant
* Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated, or both)
* Inability to stop nonsteroidal anti-inflammatory drugs (NSAIDS) for a period of 2 days before, the day of, and 2 days following administration of Alimta; 5 days before, the day of, and 2 days following administration of Alimta for long-acting NSAIDS