Increased antitumor activity in combined treatment TS-1 and docetaxel. A preclinical study using gastric cancer xenografts

As TS-1 and docetaxel (TXT) have different mechanisms of antitumor activity, the combination therapy is expected to have a higher response. Human gastric cancer xenografts SC-2, St-40, and SC-4 inoculated into nude rats were treated with TS-1 alone (TS-1 12 mg/kg/day, day 1-14), TXT alone (TXT 2 mg/kg/day, day 1 or day 8), and combination of both drugs. TS-1 alone showed antitumor activity against three tumors (growth inhibition rate (IR): SC-2 (38.6 and 40.5%), St-40 (54.5%), SC-4 (55.1%)). TXT was effective with minimal toxicity, especially on day 1 of administration (IR at day 1 administration: SC-2 (51.7%), St-40 (42.1%), SC-4 (46.3%)). In the combined TS-1 and TXT group, antitumor activity increased at day 1 and at day 8 TXT administration (IR at day 1 administration: SC-2 (68.4%), St-40 (72.5%), SC-4 (76.0%)). Weight loss of TS-1 and day 1 TXT administration was the same as that of TS-1 alone. TS-1 and TXT showed no pharmacokinetic interaction. Compared with 5-fluorouracil and cisplatin treatment, combined therapy with TS-1 and TXT showed the same antitumor activity and toxicity. Combined therapy with TS-1 and TXT showed enhanced antitumor activity compared with monotherapy of each drug. The outpatient-based treatment of this combination is worth investigating.