Phase III Study of S-1 + Cisplatin vs Cisplatin in Cervical Cancer

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.

Eligibility Criteria:
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.