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: Mamoru Nukatsuka, Hitoshi Saito, Kazuki Sakamoto, Fumio Nakagawa, Junji Uchida, Takashi Kobunai, Kazuyoshi Shiraishi, Teiji Takechi
• Journal: Anticancer research (Anticancer Res) Vol. 32 Issue 7 Pg. 2807-12 (Jul 2012) ISSN: 1791-7530 [Electronic] Greece
• PMID: 22753741 (Publication Type: Journal Article)

Chemical References

• Drug Combinations
• Organoplatinum Compounds
• Oxaliplatin
• Deoxycytidine
• S 1 (combination)
• Tegafur
• Oxonic Acid
• Capecitabine
• Fluorouracil

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Capecitabine
• Colorectal Neoplasms (drug therapy)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Drug Administration Schedule
• Drug Combinations
• Drug Resistance, Neoplasm
• Fluorouracil (administration & dosage, analogs & derivatives, pharmacology)
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Organoplatinum Compounds (administration & dosage)
• Oxaliplatin
• Oxonic Acid (administration & dosage)
• Tegafur (administration & dosage)
• Xenograft Model Antitumor Assays