Pemetrexed as Second-Line Therapy in Treating Patients With Hormone Refractory Prostate Cancer

OUTLINE: This is a multi-center study.

• Pemetrexed 500mg/m2 will be administered intravenously over approximately 10-minutes on Day 1 of a 21-day cycle.
• Folic Acid (350-1000 mcg. PO daily) will be taken by patients to reduce toxicity. At least 5 daily doses of folic acid must be taken during the 7-day period preceding the first dose of pemetrexed, and dosing should continue during the full course of therapy and for 21 days after the last dose of pemetrexed.
• Vitamin B12 (1000 µg) will be administered as an intramuscular injection during the week preceding the first dose of pemetrexed and every 3 cycles thereafter. Subsequent vitamin B12 injections may be given the same day as pemetrexed.

Performance Status: Karnofsky Performance Status 70-100

Life expectancy > 12 weeks

Hematopoietic:

• Absolute Neutrophil Count (ANC) > 1500/mm3
• Platelet count > 100,000/mm3
• Hemoglobin > 9 g/dL

Hepatic:

• Bilirubin < 1.5 X upper limit of normal (unless due to Gilbert's disease)
• Alkaline phosphatase and Alanine Transanimase (ALT) (SGPT) < 3 X upper limit of normal (ULN); may be < 5 X ULN for patients with liver metastases. Alkaline phosphatase may be any value for patients with bone metastases.

Renal:

• Calculated creatinine clearance >45 mL/min based on the standard Cockroft and Gault formula

Cardiovascular:

• No congestive heart failure requiring therapy or New York Heart Association (NYHA) class II or greater or active angina or known myocardial infarction within 12 months prior to study
• No unstable angina, uncontrolled congestive heart failure, or unstable symptomatic arrhythmia requiring medication within 6 months prior to being registered for protocol therapy
• Subjects with chronic atrial arrhythmia, i.e., atrial fibrillation, paroxysmal supraventricular tachycardia, or controlled hypertension are eligible

Pulmonary:

• Not specified

Inclusion criteria

• Histologically documented adenocarcinoma of the prostate
• Clinically refractory or resistant to hormone therapy as assessed by progression following at least one hormonal therapy (orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist)
• One prior taxane based chemotherapy regimen for HRPC
• Documented progression of disease after one taxane based prior chemotherapy regimen for HRPC. Progression is defined as at least one of the following:
• An increase in PSA > 50% over nadir value on prior Taxane-based therapy
• Progression of measurable disease as defined by RECIST
• Progression of bone disease as defined by the appearance of one or more new bone lesions or worsening symptoms
• Orchiectomy or testosterone levels < 50 ng/dL maintained by LHRH agonist
• Prior chemotherapy, or other experimental anticancer agents must be completed > 4 weeks prior to being registered for protocol therapy
• Palliative radiotherapy must be completed at least 14 days prior to registration.

Exclusion criteria

• Intravenous radio-isotopes therapy must be completed at least 6 weeks prior to registration
• No brain metastasis that are untreated and/or not controlled and/or still requiring corticosteroids
• No history of other malignancies within 5 years prior to being registered for protocol therapy, except for adequately treated basal or squamous cell skin cancer
• No history of uncontrolled psychiatric illness or serious systemic disease, including active infection, uncontrolled hypertension
• No surgery or significant traumatic injury within 21 days prior to being registered for protocol therapy
• Patients must be willing to interrupt aspirin or other non-steroidal anti-inflammatory agents for a 5-day period (8 day period for long acting agents such as piroxicam)
• Patients must be willing to take folic acid or vitamin B12 supplementation