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Article

Factors predicting the response to oral fluoropyrimidine drugs: A phase II trial on the individualization of postoperative adjuvant chemotherapy using oral fluorinated pyrimidines in stage III colorectal cancer treated by curative resection (ACT-01 Study)

  • Authors:
    • Takeo Mori
    • Masayuki Ohue
    • Yasumasa Takii
    • Tadashi Hashizume
    • Tomoyuki Kato
    • Kenjiro Kotake
    • Toshihiko Sato
    • Toshiro Tango
  • View Affiliations / Copyright

    Affiliations: Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital, Tokyo, Japan, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan, Niigata Cancer Center Hospital, Niigata, Japan, Mutsu General Hospital, Aomori, Japan, Aichi Cancer Center Hospital, Nagoya, Japan, Tochigi Cancer Center, Utsunomiya, Japan, Yamagata Prefectural Central Hospital, Yamagata, Japan, Center for Medical Statistics, Tokyo, Japan
  • Pages: 437-444
    |
    Published online on: December 10, 2012
       https://doi.org/10.3892/or.2012.2177
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Abstract

We evaluated the predictive relevance of several biomarkers on the survival of patients with stage III colorectal cancer treated with adjuvant chemotherapy of oral fluoropyrimidines. This was a multicenter phase II trial on adult patients with histologically confirmed resected stage III (Dukes' C) colorectal cancer. Patients received oral doxifluridine (800 mg/m2/day) in 3 divided doses, or oral uracil/tegafur (UFT) (400 mg/m2/day) in 2 divided doses for 5 days, every 7 days for 12 months with a 5-year follow-up. Outcome measures were disease-free survival and tissue markers [thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) protein levels and TP, DPD, thymidylate synthase (TS) and orotate phosphoribosyltransferase (OPRT) mRNA levels in tumor samples and TS tandem-repeat type in blood samples]. There was a significant association between the intratumoral TP/DPD enzyme ratio and disease-free survival when the model included the drug, the parameter and the interactions between them [hazard ratio (HR)=2.76; P=0.00469]. The 5-year disease-free survival rate was statistically significantly higher in patients with high TP/DPD ratios [median ≥2.63: 71.9%; 95% confidence interval (CI) 61.4-80.0] compared to patients with low TP/DPD ratios (<2.63: 57.0%; 95% CI 46.3-66.3) (log-rank P=0.0277) following adjuvant therapy with oral fluoropyrimidines. No significant association was observed between the intratumoral TP/DPD enzyme ratio (cut-off value 2.0) and the disease-free survival rate in the doxifluridine group; primary endpoint (log-rank P=0.6850). The magnitude of the intratumoral TP/DPD enzyme ratio may be a potential indicator for the individualization of postoperative adjuvant chemotherapy with oral fluoropyrimidines for stage III colorectal cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Mori T, Ohue M, Takii Y, Hashizume T, Kato T, Kotake K, Sato T and Tango T: Factors predicting the response to oral fluoropyrimidine drugs: A phase II trial on the individualization of postoperative adjuvant chemotherapy using oral fluorinated pyrimidines in stage III colorectal cancer treated by curative resection (ACT-01 Study). Oncol Rep 29: 437-444, 2013.
APA
Mori, T., Ohue, M., Takii, Y., Hashizume, T., Kato, T., Kotake, K. ... Tango, T. (2013). Factors predicting the response to oral fluoropyrimidine drugs: A phase II trial on the individualization of postoperative adjuvant chemotherapy using oral fluorinated pyrimidines in stage III colorectal cancer treated by curative resection (ACT-01 Study). Oncology Reports, 29, 437-444. https://doi.org/10.3892/or.2012.2177
MLA
Mori, T., Ohue, M., Takii, Y., Hashizume, T., Kato, T., Kotake, K., Sato, T., Tango, T."Factors predicting the response to oral fluoropyrimidine drugs: A phase II trial on the individualization of postoperative adjuvant chemotherapy using oral fluorinated pyrimidines in stage III colorectal cancer treated by curative resection (ACT-01 Study)". Oncology Reports 29.2 (2013): 437-444.
Chicago
Mori, T., Ohue, M., Takii, Y., Hashizume, T., Kato, T., Kotake, K., Sato, T., Tango, T."Factors predicting the response to oral fluoropyrimidine drugs: A phase II trial on the individualization of postoperative adjuvant chemotherapy using oral fluorinated pyrimidines in stage III colorectal cancer treated by curative resection (ACT-01 Study)". Oncology Reports 29, no. 2 (2013): 437-444. https://doi.org/10.3892/or.2012.2177
Copy and paste a formatted citation
x
Spandidos Publications style
Mori T, Ohue M, Takii Y, Hashizume T, Kato T, Kotake K, Sato T and Tango T: Factors predicting the response to oral fluoropyrimidine drugs: A phase II trial on the individualization of postoperative adjuvant chemotherapy using oral fluorinated pyrimidines in stage III colorectal cancer treated by curative resection (ACT-01 Study). Oncol Rep 29: 437-444, 2013.
APA
Mori, T., Ohue, M., Takii, Y., Hashizume, T., Kato, T., Kotake, K. ... Tango, T. (2013). Factors predicting the response to oral fluoropyrimidine drugs: A phase II trial on the individualization of postoperative adjuvant chemotherapy using oral fluorinated pyrimidines in stage III colorectal cancer treated by curative resection (ACT-01 Study). Oncology Reports, 29, 437-444. https://doi.org/10.3892/or.2012.2177
MLA
Mori, T., Ohue, M., Takii, Y., Hashizume, T., Kato, T., Kotake, K., Sato, T., Tango, T."Factors predicting the response to oral fluoropyrimidine drugs: A phase II trial on the individualization of postoperative adjuvant chemotherapy using oral fluorinated pyrimidines in stage III colorectal cancer treated by curative resection (ACT-01 Study)". Oncology Reports 29.2 (2013): 437-444.
Chicago
Mori, T., Ohue, M., Takii, Y., Hashizume, T., Kato, T., Kotake, K., Sato, T., Tango, T."Factors predicting the response to oral fluoropyrimidine drugs: A phase II trial on the individualization of postoperative adjuvant chemotherapy using oral fluorinated pyrimidines in stage III colorectal cancer treated by curative resection (ACT-01 Study)". Oncology Reports 29, no. 2 (2013): 437-444. https://doi.org/10.3892/or.2012.2177
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