Combined Use of Raltitrexed and S-1 as Treatment for Patients With Metastasizing Colorectal Cancer

Exclusion Criteria

• •1. Prior treatment with raltitrexed and gimeracil and oteracil potassium
• •2. Systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy and hormonal therapy during this trial or within 4 weeks (or 6 weeks for mitomycin C) before starting to receive study medication.
• •3. Alcohol or drug addictions
• •4. Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)\]
• •5. Any history of or currently known brain metastases
• •6. Multiple primary colorectal carcinoma
• •7. Concomitant participation or participation within the last 30 days in another clinical trial
• •8. There is an important organ failure or other serious diseases, including coronary artery disease, symptomatic cardiovascular disease or myocardial infarction within 12 months; serious neurological or psychiatric history; severe infection; actively disseminated vascula blood coagulation.
• •9. Extended field radiotherapy within 4 weeks or limited field radiotherapy within 2 weeks prior to randomization. Subjects must have recovered from all therapy-related toxicities. The site of previous radiotherapy should have evidence of progressive disease if this is the only site of disease.
• •10. Pregnant or breast-feeding subjects. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of treatment.
• •11. Pleural effusion or ascites that causes respiratory compromise (≥Common Terminology Criteria for Adverse Events \[CTCAE\]) Grade 2 dyspnea)
• •12. Subjects unable to swallow oral medications
• •13. Known history of human immunodeficiency virus (HIV) infection