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.
Takahashi
Ikuo
I
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan. takahasii@fukuokae2.hosp.go.jp
Emi
Yasunori
Y
Kakeji
Yoshihiro
Y
Uchida
Junji
J
Fukushima
Masakazu
M
Maehara
Yoshihiko
Y
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077143:Docetaxel; D004334:Drug Administration Schedule; D004338:Drug Combinations; D006801:Humans; D008297:Male; D010094:Oxonic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011725:Pyridines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude; D013274:Stomach Neoplasms / Q000097:blood / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005641:Tegafur / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014183:Transplantation, Heterologous
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D004338:Drug Combinations; D011725:Pyridines; D043823:Taxoids; C079198:S 1 (combination); D005641:Tegafur; D000077143:Docetaxel; D010094:Oxonic Acid