Trial of S-1 Plus Cisplatin (SP) Versus Gemcitabine Plus Cisplatin (GP) in Advanced Biliary Tract Adenocarcinoma

• Response rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  Response to chemotherapy will be assessed using RECIST 1.0 criteria.
• Toxicities [ Time Frame: Up to 24 months ] [ Designated as safety issue: Yes ]
  Toxicities associated chemotherapy will be assessed and categorized using NCI CTCAE v3.0. The types of toxicities and the proportions of patients who experience each toxicity will be described.
• overall survival [ Time Frame: up to 36 months ] [ Designated as safety issue: No ]
  Overall survival is calculated from the date of enrollment to the date of death from any cause.

To select a better agent between S-1 or gemcitabine in combination with cisplatin for the conventional chemotherapy platform for future development in advanced Biliary Tract Adenocarcinoma (BTA), the investigators conduct a randomized phase II trial of S-1 and cisplatin (SP) versus gemcitabine and cisplatin (GP) as first line therapy in advanced BTA.

• Drug: S-1 plus cisplatin
  S-1 40 mg/m2 D1-D14 Cisplatin 60 mg/m2 D1 every 3 weeks
• Drug: Gemcitabine plus Cisplatin
  Gemcitabine 1000 mg/m2 IV D1, D8 Cisplatin 60 mg/m2 IV D1 Every 3 weeks

• Experimental: SP treatment
  S-1 plus cisplatin combination chemotherapy
  Intervention: Drug: S-1 plus cisplatin
• Active Comparator: GP treatment
  Gemcitabine plus Cisplatin combination chemotherapy
  Intervention: Drug: Gemcitabine plus Cisplatin

Inclusion Criteria:

1. Pathologically proven biliary adenocarinoma
2. Age > 18
3. Evaluable disease
4. ECOG performance status of 2 or better
5. No prior exposure to chemotherapy, but adjuvant chemotherapy (or chemoradiotherapy) completed 6 moths or more before study enrollment is allowed
6. Adequate bone marrow function A. WBCs > 4,000/µL, absolute neutrophil count [ANC]>1,500/µL B. Hemoglobin >9.0 g/dL C. Platelets > 100,000/µL
7. Adequate kidney function (creatinine<1.5 mg/dL)
8. Adequate liver function (bilirubin<1.5 mg/dL [< 2.5 mg/dL for obstructive jaundice with adequately decompressed bile duct obstruction], transaminases levels<3 times the upper normal limit, and serum albumin of >2.5 mg/dL)
9. No serious medical or psychological condition that would preclude study treatment
10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Exclusion Criteria:

1. Other tumor type than adenocarcinoma
2. Evidence of GI bleeding or GI obstruction
3. Presence or history of CNS metastasis
4. Pregnancy or breastfeeding
5. Other serious illness or medical conditions
6. Axial skeletal radiotherapy within 6 months
7. Neuropathy grade 2 or worse