Impact of 5-fluorouracil metabolizing enzymes on chemotherapy in patients with resectable colorectal cancer

Ochiai,Takumi; Umeki,Masahiko; Miyake,Hiroshi; Iida,Tatsumi; Okumura,Minoru; Ohno,Kazuhide; Sakamoto,Masashi; Miyoshi,Nobukazu; Takahashi,Masahiko; Tsumura,Hidenori; Tokunaga,Yukihiko; Naitou,Haruhiko; Fukui,Takuji

doi:10.3892/or.2014.3299

Impact of 5-fluorouracil metabolizing enzymes on chemotherapy in patients with resectable colorectal cancer

Authors:
- Takumi Ochiai
- Masahiko Umeki
- Hiroshi Miyake
- Tatsumi Iida
- Minoru Okumura
- Kazuhide Ohno
- Masashi Sakamoto
- Nobukazu Miyoshi
- Masahiko Takahashi
- Hidenori Tsumura
- Yukihiko Tokunaga
- Haruhiko Naitou
- Takuji Fukui
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Affiliations: Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo 125-8512, Japan, Department of Surgery, Hyogo Prefectural Awaji Medical Center, Hyogo 656-0021, Japan, Department of Surgery, Kasukabe Municipal Hospital, Saitama 344-0067, Japan, Department of Surgery, Nishimino Kosei Hospital, Gifu 503-131, Japan, Department of Surgery, Hitachi General Hospital, Ibaragi 317-0077, Japan, Department of Surgery, Matsudo City Hospital, Chiba 271-0064, Japan, Department of Surgery, Mitsui Memorial Hospital, Tokyo 101-8643, Japan, Department of Surgery, Kure Kyosai Hospital, Hiroshima 737-0811, Japan, Department of Surgery, Hokkaido P.W.F.A.C Asahikawa-Kosei General Hospital, Hokkaido 078-8211, Japan, Department of Surgery, Koshigaya Municipal Hospital, Saitama 343-0023, Japan, Department of Surgery, Japanpost Osaka-kita Teishin Hospital, Osaka 530-0016, Japan, Department of Surgery, Hokkaido Cancer Center, Hokkaido 003-0804, Japan, Department of Surgery, Kariya Toyota General Hospital, Aichi 448-8505, Japan
Published online on: July 2, 2014 https://doi.org/10.3892/or.2014.3299
Pages: 887-892
Copyright: © Ochiai et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Although 5-fluorouracil (5-FU) is an important drug for colorectal cancer (CRC) treatment, no useful biomarker is currently available to predict treatment response. Since 5-FU is converted into active or inactive forms by orotate phosphoribosyltransferase (OPRT) or dihydropyrimidine dehydrogenase (DPD), a correlation between these enzymes and response to 5-FU has been suggested. However, such a correlation has not been investigated prospectively. Therefore, in the present study, we aimed to prospectively evaluate whether OPRT and DPD were predictive factors of the response to 5-FU treatment in patients with resectable CRC. The present investigation was designed as a multicenter prospective cohort study. OPRT and DPD activities were assessed in biopsy samples, obtained surgically from patients with resectable CRC. The OPRT/DPD ratio was calculated and the cut-off values for this ratio were determined for 5-year disease-free survival (DFS) and overall survival (OS). Patients were treated with 5-FU/leucovorin (LV) regimens and oral 5-FU. The endpoint of this study was the correlation between the OPRT/DPD ratio and 5-year DFS and OS. The cut-off value for the OPRT/DPD ratio was determined by using the maximum χ2 statistic method against 5-year DFS and OS. Sixty-eight patients were enrolled from July 2003 to May 2005. The median follow-up period was 1925 days. The OPRT/DPD ratio cut-off values for 5-year DFS and OS were 0.015 and 0.013, respectively. During the 5-year DFS and OS periods, patients with higher cut-off values had a better prognosis than those with lower ratios (P=0.03 and 0.02, respectively). In conclusion, our results suggest that the OPRT/DPD ratio could be a predictive factor for response to 5-FU/LV adjuvant chemotherapy.

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