• Adverse events [ Time Frame: The follow up period will be five years after the last dose has been administered. ] [ Designated as safety issue: Yes ]
• Antitumor effects [ Time Frame: The follow up period will be five years after the last dose has been administered. ] [ Designated as safety issue: No ]
• Time to treatment failure [ Time Frame: The follow up period will be five years after the last dose has been administered. ] [ Designated as safety issue: Yes ]
• Survival rate [ Time Frame: The follow up period will be five years after the last dose has been administered. ] [ Designated as safety issue: No ]

• Adverse events
• Antitumor effects
• Time to treatment failure
• Survival rate

To investigate and compare the efficacy and safety of TS-1 vs. Xeloda as primary chemotherapy in patients with inoperable or recurrent breast cancer.

The incidence of breast cancer is increasing in Japan: 33,676 women were diagnosed with breast cancer in 2001, making it the leading cause of cancer among women since 1995. Statistical database in Exel format/outline of health welfare statistics from the Ministry of Labor, Health, and Welfare show that the number of deaths from breast cancer was 9,806 in 2003. Because the ten-year survival rate is about ninety percent in Stages 0 and I breast cancer patients, detection and treatment at an earlier stage can lead to higher survival rates. However, the recurrence rate increases as the disease progresses. In addition, about thirty percent of all breast cancer patients are believed to have recurrent disease. Thus, developing treatments against recurrence may be an important task.

The Guideline for Breast Cancer Treatment, 2004 version, recommends chemotherapy, including anthracyclines or taxanes as a first-line chemotherapy for metastatic or recurrent (grade B recommendation) breast cancer. In a second-line therapy recommended for metastatic or recurrent diseases, the Guideline reports that a combination of capecitabine, a 5Fu derivative (an oral chemotherapy of pyrimidine fluorides approved in 2003) with docetaxel is superior to docetaxel alone for improving survival. This regimen is recommended for patients with cardiac malfunction who cannot be treated with anthracyclines (grade B recommendation). However, data are lacking to support capecitabine as a standard regimen as a second-line therapy; its efficacy needs verification and further study. Accordingly, this study is designed to investigate the efficacy and safety of TS-1 alone, an oral pyrimidine fluoride, to which an indication of "inoperable or recurrent breast cancer" was added, as a first-line therapy in patients with inoperable or recurrent breast cancer by comparing it with Xeloda (capecitabine) alone, which is already approved of the same indication.

• Drug: Capecitabine
• Drug: TS-1

• Active Comparator: Capecitabine (Xeloda): 1600 mg/m2 orally bid daily for day 1 through day 21 followed by 7-day washout; repeat this as a course.
• Experimental: TS-1: 80 mg/m2 orally bid daily for day 1 through day28 followed by 14-day washout; repeat this as a course.

Inclusion Criteria:

• Biopsy-diagnosed breast cancer with metastasis in multiple organs
• Performance Status (World Health Organization :WHO) 0-2

• Functions below are maintained in major organs:

  • Leukocyte count: 4,000/mm3 to 12,000/mm3
  • Neutrophil count: >2,000/mm3 or more
  • Platelet count: <100,000/mm3 or more
  • Hemoglobin: >9.5 g/dL
  • Total bilirubin: >1.5 mg/dL
  • AST(GOT): within twice a normal upper value in an institution
  • AST(GPT): within twice a normal upper value in an institution
  • BUN: < 25 mg/dL
  • Creatinine: within a normal upper value in the institution
  • 24 hours creatinine clearance: >50 mL/min (using the Cockcroft-Gault formula)
  • Women's Ccr = Body weight x (140-Age)/(72 x Serum creatinine) x 0.85
• Written informed consent will be obtained for patients for entering this study

Exclusion Criteria:

• Patients with synchronous multiple cancers
• Complicated with infection
• Fever from suspected infection
• Metastasis to the central nerve system
• A history of ischemic cardiac diseases
• Active gastrointestinal ulcer
• Severe nerve disorder
• Women who are potentially pregnant, pregnant, or breast-feeding
• Severe drug allergy
• Severe suppression of the bone marrow
• Severe renal disorder
• Being treated with other pyrimidine fluoride antineoplastic agents (including any combination therapy)
• Being treated with flucytosine
• Complicated with the infection onset which a study doctor assesses to be inappropriate for this study