Oxaliplatin and S-1 (OS) Versus Oxaliplatin and Capecitabine (XELOX) for Advanced Colorectal Cancer

A Randomized Phase II Study of Oxaliplatin and S-1 (OS) Versus Oxaliplatin and Capecitabine (XELOX) in Patients With Advanced or Recurrent Colorectal Cancer

The aim of this study is to compare the activity and safety of Oxaliplatin and S-1 (OS) and Oxaliplatin and Capecitabine (XELOX) in patients with advance or recurrent colorectal cancer.

Oxaliplatin and oral fluoropyrimidines (capecitabine or S-1) are active agents for colorectal cancer. Recent a phase II trial of combination chemotherapy of oxaliplatin with S-1 (OS) and several phase II trial of combination chemotherapy of oxaliplatin with capecitabine (XELOX) demonstrated good activity and mild toxicity in advanced colorectal cancer. Oxaliplatin and S-1 or capecitabine have distinct mechanisms of action and no overlap of key toxicities. Furthermore, oxaliplatin and fluorouracil were shown to be highly synergistic, not only in preclinical models but also in subsequent clinical trials.

Inclusion Criteria:

• Histologically confirmed colorectal adenocarcinoma, initially diagnosed or recurred
• Unresectable, locally advanced or metastatic
• At least one uni-dimensional measurable lesion by RECIST criteria
• Age 18 to 75 years old
• Estimated life expectancy ≥3 months
• ECOG performance status ≤2
• Adequate bone marrow function (WBCs ≥ 4,000/µL or absolute neutrophil count ≥ 1,500/µL, platelets ≥ 100,000/µL)
• Adequate kidney function (creatinine < 1.5 mg/dL)
• Adequate liver function (bilirubin < 2.0 mg/dL, transaminase levels <2.5 times the upper normal limit)
• Written informed consent

Exclusion Criteria:

• Other tumor type than adenocarcinoma
• Previous history of chemotherapy (exception : neoadjuvant or adjuvant chemotherapy without oxaliplatin)
• Presence of CNS metastasis, psychosis, or seizure
• Obvious bowel obstruction
• Evidence of serious gastrointestinal bleeding
• Past or concurrent history of neoplasm other than colorectal adenocarcinoma, except for curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix uteri
• Pregnant or lactating women, women of childbearing potential not employing adequate contraception
• Other serious illness or medical conditions