Oncology Medical Affairs Department, Tokushima Research Center, Tokushima, Japan.
Anticancer Res. 2012 Jul;32(7):2807-12.
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 1 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 1 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.
奥沙利铂与氟尿嘧啶（5-FU）和亚叶酸联合应用，或与卡培他滨（COX）联合应用于结直肠癌的治疗是有效的。在这项实验中，我们研究了 S-1 联合奥沙利铂（SOX）组合疗法在体内对人结直肠癌细胞异种移植物的最佳联合方案和抗肿瘤活性。用人结肠癌 COL-1 荷瘤裸鼠，奥沙利铂单独在第 1 天给予总量 8.3mg/kg，单独在第 8 天给予，或在第 1 天和第 8 天给予 S-1（6.9mg/kg，第 1-14 天）分剂量给予。根据分剂量方案给予的 SOX 的抗肿瘤活性明显优于单药治疗（p<0.01），且毒性可耐受。然而，与单药治疗相比，第 8 天单独给药并不能显著增加抗肿瘤活性，而在该模型中，第 1 天单独给药则具有毒性。接下来，将 SOX 的疗效与 COX（360mg/kg，第 1-14 天）进行比较。SOX 的抗肿瘤作用明显优于 COX（p<0.01），毒性相当；此外，SOX 抑制 COL-1 肿瘤生长的时间（2.2 倍）长于 COX。SOX 对 5-FU 耐药结直肠癌细胞系 KM12C/5-FU 的抗肿瘤活性与 COX 相当。在临床试验中评估间歇性 SOX 给药可能具有重要价值。
