title: Efficacy of combination chemotherapy using oral fluoropyrimidine S-1 with oxaliplatin (SOX) against colorectal cancer in vivo.
abstract: 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.
authors: Oncology Medical Affairs Department, Tokushima Research Center, Tokushima, Japan. m-nukatsuka@taiho.co.jp
authors: Mamoru
authors: M
authors: Nukatsuka
authors: Hitoshi
authors: H
authors: Saito
authors: Kazuki
authors: K
authors: Sakamoto
authors: Fumio
authors: F
authors: Nakagawa
authors: Junji
authors: J
authors: Uchida
authors: Takashi
authors: T
authors: Kobunai
authors: Kazuyoshi
authors: K
authors: Shiraishi
authors: Teiji
authors: T
authors: Takechi
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays
chemical_list: D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000069287:Capecitabine; D005472:Fluorouracil