論文

査読有り 国際誌
2018年12月

Relationship Between Thymidine Kinase 1 Expression and Trifluridine/Tipiracil Therapy in Refractory Metastatic Colorectal Cancer: A Pooled Analysis of 2 Randomized Clinical Trials.

Clinical colorectal cancer
  • Takayuki Yoshino
  • ,
  • Kentaro Yamazaki
  • ,
  • Eiji Shinozaki
  • ,
  • Yoshito Komatsu
  • ,
  • Tomohiro Nishina
  • ,
  • Hideo Baba
  • ,
  • Akihito Tsuji
  • ,
  • Yasushi Tsuji
  • ,
  • Kensei Yamaguchi
  • ,
  • Naotoshi Sugimoto
  • ,
  • Tadamichi Denda
  • ,
  • Kei Muro
  • ,
  • Tetsuji Takayama
  • ,
  • Taito Esaki
  • ,
  • Yasuo Hamamoto
  • ,
  • Toshikazu Moriwaki
  • ,
  • Yasuhiro Shimada
  • ,
  • Masahiro Goto
  • ,
  • Norisuke Nakayama
  • ,
  • Hirofumi Fujii
  • ,
  • Takanori Tanase
  • ,
  • Atsushi Ohtsu

17
4
開始ページ
e719-e732
終了ページ
記述言語
英語
掲載種別
DOI
10.1016/j.clcc.2018.07.009

BACKGROUND: High thymidine kinase 1 (TK1) activity increases the incorporation of trifluridine (FTD) into DNA; thus, FTD antitumor activity is likely to increase in patients with high tumoral TK1 activity. To date, no established predictive biomarker to indicate the clinical benefit of FTD/tipiracil (TPI) has been identified. We aimed to determine the relationship between TK1 expression and FTD/TPI efficacy in refractory metastatic colorectal cancer. PATIENTS AND METHODS: Individual patient data from 2 randomized placebo-controlled trials were analyzed. We measured TK1 protein expression in tumor tissue samples and its relationship with FTD/TPI clinical efficacy using overall survival (OS), progression-free survival, and disease control rate. RESULTS: This study comprised 329 patients (FTD/TPI, 224; placebo, 105). FTD/TPI significantly improved OS versus placebo in the high-expression (cutoff ≥ 15%) TK1 group (median OS, 7.8 vs. 6.8 months; hazard ratio = 0.65; 95% confidence interval, 0.46-0.93; P = .018). The low-expression (cutoff < 15%) TK1 group experienced a smaller OS benefit (9.3 vs. 7.4 months; hazard ratio = 0.88; 95% confidence interval, 0.63-1.23; P = .45). For patients who received placebo, the high-expression TK1 group had a slightly worse prognosis than the low-expression TK1 group. The tendency of FTD/TPI efficacy concerning progression-free survival and disease control rate was not similar to that concerning OS between groups. CONCLUSION: Patients with high TK1 expression showed an improvement in OS when treated with FTD/TPI. Further investigations are warranted to confirm this relationship.

リンク情報
DOI
https://doi.org/10.1016/j.clcc.2018.07.009
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30172759
ID情報
  • DOI : 10.1016/j.clcc.2018.07.009
  • ISSN : 1533-0028
  • PubMed ID : 30172759

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