This study is an open-label, multicenter, multinational, two-arm, parallel randomized Phase 3 study evaluating the efficacy and safety of S-1+Cisplatin versus single-agent Cisplatin in patients with stage IVB, recurrent or persistent carcinoma of the cervix.

Japanese phase II study of S-1 in cervical cancer suggested promising response rate and good tolerability. Since recommended chemotherapy for metastatic or recurrent cervical carcinoma is either single-agent Cisplatin or Cisplatin-based combination chemotherapy, this is designed to evaluate the efficacy and safety of S-1 in combination with Cisplatin compared with single-agent Cisplatin.

Inclusion Criteria:

• Patients with histologically proven cervical carcinoma (All histological subtype will be included).

• Patients who have stage IVB, recurrent or persistent disease.

• Patients who are not amenable to curative treatment with surgery and/or radiotherapy.

• Patients who have not received chemotherapy or chemoradiotherapy after diagnosis of recurrent, persistent, or stage IVB disease.

• If the patient have received chemotherapy, radiotherapy or chemoradiotherapy as previous treatment, following interval must have elapsed from the last administration of treatment:

  1. Chemotherapy: 21 days
  2. Radiotherapy: 21 days*
  3. Chemoradiotherapy: 42 days*

If there have been residual disease in previously irradiated field and without disease progression since the (chemo) radiotherapy, 90 days must have elapsed after the last administration of irradiation.

• Patients who have adequate hematologic, hepatic and renal functions as defined below:

  • Hemoglobin: ≥ 8.0 g/dL
  • Neutrophil count: ≥ 2,000/mm^3
  • Platelet count: ≥ 100,000/mm^3
  • Total serum bilirubin: ≤ 1.5 times the upper limits of normal (ULN)
  • AST (GOT), ALT (GPT): ≤ 2.5 times the ULN. If abnormal values are associated with hepatic metastasis: ≤ 5.0 times the ULN
  • Serum creatinine: ≤ ULN or creatinine clearance: ≥ 50 ml/min

• Patients who have an ECOG performance status : 0-1.

• Age: ≥ 20 years old.

• Patients who can take pills orally.

• Patients who signed the written consent form.

Exclusion Criteria:

• Patients who have known hypersensitivity to 5-FU or Cisplatin.
• Patients who are receiving concomitant treatment with drugs interacting with S-1.
• Patients who are receiving concomitant treatment with drugs interacting with Cisplatin.
• Patients who were administered other investigational products within 30 days before the initiation of study treatment.
• Patients who were previously treated with S-1.
• Patients who had received platinum-containing chemotherapy or chemoradiotherapy and whose disease progressed during the therapy.
• Patients who suffer from active infection (e.g. fever ≥ 38°C).
• Patients who have serious complications.
• Patients with bleeding which requires hemostasis treatment.
• Patients with bilateral hydronephrosis which cannot be alleviated by ureteral stents or percutaneous drainage.
• Patients with uncontrolled pleural effusion and/or ascites requiring drainage at least twice a week.
• Patients with symptomatic brain metastasis or history of brain metastasis.
• Patients who have unmanageable bowel movement (ex. Watery stool, chronic constipation).
• Patients with active double cancer.
• Patients who are pregnant or lactating.
• Patients who are considered to be inappropriate to the subject of this study by the investigator.

A total of 364 (188 in Arm A; 176 in Arm B) received study treatment. Two patients in Arm B were excluded in the efficacy analysis, because of insufficient informed consent, and missing efficacy data.

From the date of the first treatment to 30 days after the last treatment

A total of 364 (188 in Arm A; 176 in Arm B) received study treatment. One patient in Arm B were excluded in the safety analysis, because of insufficient informed consent.