2010年12月
Synergistic antitumor activity of the SN-38-incorporating polymeric micelles NK012 with S-1 in a mouse model of non-small cell lung cancer
INTERNATIONAL JOURNAL OF CANCER
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- 巻
- 127
- 号
- 11
- 開始ページ
- 2699
- 終了ページ
- 2706
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1002/ijc.25282
- 出版者・発行元
- JOHN WILEY & SONS INC
The combination therapy of CPT-11, a prodrug of SN-38, with S-1, a dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, shows a high clinical response rate in non-small cell lung cancer (NSCLC). However, this combination causes severe toxicities such as diarrhea. Here, we investigated the advantages of treatment with the SN-38-incorporating polymeric micelles NK012 over CPT-11 in combination with S-1 in mice bearing a NSCLC xenograft in terms of antitumor activity and toxic effects, particularly intestinal toxicity. In vitro cytotoxic effects were examined in human NSCLC cell lines (A549, PC-9, PC-14, EBC-1 and H520). In vivo antitumor effects were evaluated in PC-14- and EBC-1-bearing mice after NK012 or CPT-11 administration on Days 0 and 7 and S-1 administration on Days 0-13. Pathological changes in the small intestine were also investigated. The in vitro growth inhibitory effects of NK012 were 56.8- to 622-fold more potent than those of CPT-11. NK012/S-1 treatment showed significantly higher antitumor activity both in PC-14-bearing (p = 0.0007) and EBC-1-bearing mice (p < 0.0001) than CPT-11/S-1 treatment. The deformity and decrease in the density of intestinal villi were more severe in CPT-11/S-1-treated mice than in NK012/S-1-treated mice. NK012/S-1 combination is a promising candidate regimen against NSCLC without inducing toxicities such as severe diarrhea and therefore warrants clinical evaluation.
- リンク情報
- ID情報
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- DOI : 10.1002/ijc.25282
- ISSN : 0020-7136
- Web of Science ID : WOS:000283609500022