['metastatic colorectal cancer']
['s-1+leucovorin']

        Inclusion Criteria:

          1. histologically or cytologically confirmed colorectal adenocarcinoma;

          2. metastatic and unresectable disease;

          3. presence of at least one measurable tumor lesion which is defined as lesion that can
             be measured in at least one dimension (longest diameter) with a minimum size of:

               1. 10mm by CT scan and MRI (no less than double the slice thickness and a minimum of
                  10mm);

               2. 20mm by conventional techniques;

          4. previously treatment to

               1. fluoropyrimidine, oxaliplatin and irinotecan;

               2. at least one targeted therapy

          5. adequate hematopoietic function which is defined as below:

               1. hemoglobin ≥ 9 g/dL;

               2. absolute neutrophil count (ANC) ≥ 1,500/mm3;

               3. platelet count ≥ 100,000/mm3;

          6. adequate hepatic function which is defined as below:

               1. total bilirubin ≤ 2 times upper limit of normal (ULN);

               2. hepatic transaminases (ALT and AST) ≤ 3 x ULN. If there are known liver
                  metastases, ALT or AST must be ≤ 5 x ULN;

          7. adequate renal function which is defined as below:

             a. serum creatinine ≤ 1.5 x ULN;

          8. age of 20 years or above;

          9. ECOG performance status 0-2;

         10. life expectancy of at least 12 weeks;

         11. ability to take oral medication;

         12. ability to understand and willingness to sign a written informed consent document.

        Exclusion Criteria:

          1. history or known presence of brain metastasis;

          2. presence of mental disease or psychotic manifestation;

          3. significant medical conditions that is contraindicated to study medication or render
             patient at high risk from treatment complications based on investigator's discretion;

          4. presence of diarrhea ≥ grade 2 in common terminology criteria for adverse event
             version 4.0 (CTCAE v4.0);

          5. other malignancy within the past 5 years (different site or histology) except for
             adequately treated basal or squamous cell skin cancer or cervical cancer in situ;

          6. recent (within 30 days prior to study treatment) treatment of another investigational
             drug;

          7. pregnant women or nursing mothers, or positive pregnancy test for women of
             childbearing potential. Patients with childbearing potential should have effective
             contraception for both the patient and his or her partner during the study.
      