• To evaluate the use of pemetrexed for 3 cycles prior to surgery [ Time Frame: 3 cycles ] [ Designated as safety issue: Yes ]
  

• Pathological response rate (pCR) [ Time Frame: surgical complete response post chemotherapy ] [ Designated as safety issue: No ]
  
• Pharmacology toxicity [ Time Frame: every cycle ] [ Designated as safety issue: Yes ]
  

Inclusion Criteria:

• no prior therapy for rectal cancer
• pathological/ cytological diagnosis of adenocarcinoma of the rectum. Patients must have operable rectal cancer that is amenable to surgery.
• adequate organ function
• ECOG Performance status 0 or 1
• signed informed consent
• at least 18 years of age
• surgically sterile, postmenopausal (women) or compliant with a medically approved contraceptive regimen during and for 6 months after the treatment.

Exclusion Criteria:

• concurrent administration of any other anti-tumor therapy
• treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry
• serious concomitant systemic disorders
• previously completed or withdrawn from this study
• pregnant or breast-feeding
• second primary malignancy
• history of significant neurological or mental disorder, including seizures or dementia
• inability to interrupt aspirin or other nonsteroidal anto-inflammatory drugs (NSAIDs)
• presence of clinically relevant third space fluid collections that cannot be controlled by drainage or other procedure prior to the study entry
• inability or unwillingness to take folic acid, vitamin B12 or dexamethasone