Efficacy of Combination Chemotherapy Using Oral Fluoropyrimidine S-1 with Oxaliplatin (SOX) against Colorectal Cancer In Vivo

Oxaliplatin is effective when used with 5-fluorouracil (5-FU) and leucovorin, or with capecitabine (COX) for the treatment of colorectal cancer. In this experiment, we investigated the optimal combination schedule and antitumor activity of oral S-1 with oxaliplatin combination therapy (SOX) against human colorectal cancer xenografts in vivo. Using human colon cancer COL-1-bearing nude mice, oxaliplatin was administered at a total dose of 8.3 mg/kg on day I alone, on day 8 alone, or in divided doses administered on days 1 and 8 with S-1 (6.9 mg/kg, days 1-14). The antitumor activity of SOX, administered according to the divided schedule was significantly superior to both monotherapies (p<0.01), and the toxicity was tolerable. However, administration on day 8 alone failed to significantly increase the antitumor activity, when compared with that of monotherapy, while administration on day I alone was toxic in this model. Next, the efficacy of SOX was compared with that of COX (360 mg/kg, days 1-14). The antitumor effect of SOX was significantly superior to that of COX (p<0.01), with an equivalent toxicity; moreover SOX suppressed COL-1 tumor growth for a longer period of time (2.2 times) than did COX. The antitumor activity of SOX against the 5-FU-resistant colorectal cancer cell line KM12C/5-FU was equivalent to that of COX. The evaluation of intermittent SOX administration in a clinical trial might be of critical value.