Study of S-1 and Oxaliplatin (SOX) Versus Capecitabine and Oxaliplatin (COX) in Patients With Advanced Colorectal Cancer

• The urgent need for new effective therapy with better safety profile for metastatic colorectal cancer patients and promising results observed so far in trials with S-1 combined with oxaliplatin in gastrointestinal cancer including colorectal cancer strongly warrants the comparison of S-1 combined with oxaliplatin to capecitabine combination with oxaliplatin acknowledged as a standard regimen in a first-line treatment for advanced colorectal cancer patients.
• Recently, a Phase I study was completed, indicating recommended dose as S-1 100 mg/m2/day1-14 and oxaliplatin (130 mg/m2/day1), repeated every 3 weeks. However, in the phase II study using the above recommended dose, delayed toxicities of thrombocytopenia and anemia were observed. These delayed toxicities were also reported in a phase II study using S-1 90 mg/m2/day plus oxaliplatin 130 mg/m2/day1 in advanced gastric cancer. At 2007 GI ASCO, the interim data of S-1(80 mg/m2/day1-14) plus oxaliplatin (130 mg/m2/day1) combination, repeated every 3 weeks, was presented, showing promising antitumor activity with favourable safety profile. Among 18 patients, there were only two patients with Grade 3 thrombocytopenia and one with Grade 3 neutropenia. Response rate was 57.1 % and disease control rate was 92.9 %. Considering these results and Japanese data which showed that enhanced efficacy was not observed with S-1 over 90 mg/m2/day and oxaliplatin combination, S-1 80 mg/m2/day 1-14 and oxaliplatin 130 mg/m2/D1, repeated every 3 weeks, will be tested in this study.

Inclusion criteria

• Histologically documented colorectal adenocarcinoma
• Age over 18 years old
• Performance status (ECOG scale): 0-2
• Measurable or evaluable disease
• Patients can take food and drugs orally
• Adequate organ functions
• Life expectancy ≥ 3 months
• Patients should sign a written informed consent before study entry

Exclusion criteria

• Tumor type other than adenocarcinoma
• Second primary malignancy
• Prior systemic therapy (for instance, cytotoxic chemotherapy or active/passive immunotherapy) for advanced or metastatic colorectal cancer
• Adjuvant or neo-adjuvant treatment for non-metastatic (M0) disease has been completed within 6 months prior to initiation of study treatment.
• Prior radiotherapy was administered to target lesions selected for this study, or radiotherapy to the non-target lesions has been completed within 4 weeks before randomization.
• Presence of CNS metastasis
• Obvious peritoneal seeding or bowel obstruction disturbing oral intake
• Symptomatic peripheral neuropathy
• Major surgery within 4 weeks prior to study treatment start, or lack of complete recovery from the effects of major surgery. The patient received curative operation or RFA for metastatic disease.
• Serious illness or medical conditions
• Receiving a concomitant treatment with drugs interacting with S-1, capecitabine or oxaliplatin, as follows;flucytosine, a fluorinated pyrimidine antifungal agent phenytoin warfarin etc.
• Received any investigational drug or agent/procedure, i.e. participation in another trial within 4 weeks before beginning treatment with study drug.
• Pregnant or lactating woman
• Women of child bearing potential not using a contraceptive method
• Sexually active fertile men not using effective birth control during medication of study drug and up to 6 months after completion of study drug if their partners are women of child-bearing potential
• Any patients judged by the investigator to be unfit to participate in the study