Inclusion Criteria:

1. Histologically confirmed colorectal carcinoma with inoperable, locally advanced, or
metastatic disease, not amenable to curative therapy

2. Measurable disease or non-measurable but assessable disease according to the Response
Evaluation Criteria in Solid Tumors (RECIST)

3. Patients with no previous treatment (radiotherapy or chemotherapy). Patients who have
received postoperative adjuvant chemotherapy are eligible if relapse is diagnosed
more than 180 days after the end of such treatment.

Preoperative or postoperative irradiation (<30 Gy) for rectal cancer is possible

4. Age >20 years

5. Life expectancy of at least 3 months

6. ECOG PS of 0 or 1

7. Adequate function of major organs as defined below:

1. Hemoglobin >9.0 g/dL

2. White blood cell count >3,000/mm3

3. Neutrophil count >1,500/mm3

4. Platelet count >100,000/mm3

5. Total bilirubin <1.5 mg/dL

6. AST and ALT <100 U/L (<200 U/L in patients with liver metastasis)

7. Serum creatinine <1.2 mg/dL

8. Creatinine clearance estimate by the Cockcroft-Gault method >50 mL/min (reduce
initial dosage by one step if ≥50 but <80 mL/min)

8. Able to take capsules orally.

9. No electrocardiographic abnormalities within 28 days before enrollment that would
clinically preclude the execution of the study, as judged by the investigator.

10. Voluntary written informed consent.

Exclusion Criteria:

1. Serious drug hypersensitivity or a history of drug allergy

2. Active double cancer

3. Active infections (e.g., patients with pyrexia of 38℃ or higher)

4. History of gastrointestinal perforation, intestinal tract paralysis, or ileus within
1 year.

5. Uncontrolled hypertension

6. Serious complications (e.g., pulmonary fibrosis, interstitial pneumonitis, heart
failure, renal failure, hepatic failure, or poorly controlled diabetes)

7. Moderate or severe ascites or pleural effusion requiring treatment

8. Watery diarrhea

9. Treatment with flucytosine or atazanavir sulfate

10. Metastasis to the CNS

11. Pregnant women, possibly pregnant women, women wishing to become pregnant, and
nursing mothers. Men who are currently attempting to conceive children.

12. Severe mental disorder

13. Continuous treatment with steroids

14. Urine dipstick for proteinuria should be <2+

15. Patient with a past history of thrombosis, cerebral infarction, myocardial
infarction, or pulmonary embolism

16. Major surgical procedure, open biopsy, or clinically significant traumatic injury
within 4 weeks

17. Long-term daily treatment with aspirin (>325 mg/day)

18. History or evidence of inherited bleeding diathesis or coagulopathy with the risk of
bleeding

19. Judged ineligible for participation in the study by the investigator for safety
reasons.