Identifying Prognostic Factors in Patients Receiving Tegafur-Uracil for Stage II Colon Cancer That Was Completely Removed By Surgery

Identification of the Prognostic Factors of Stage II Colon Cancer Patients Receiving Adjuvant Chemotherapy With UFT

RATIONALE: Studying samples of tumor tissue in the laboratory from patients with cancer may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors predict which patients will respond to treatment.

PURPOSE: This laboratory study is looking at prognostic factors in patients receiving tegafur-uracil for stage II colon cancer that was completely removed by surgery.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: UFT adjuvant chemotherapy

Detailed Description

OBJECTIVES:

• Identify the prognostic factors in patients with curatively resected stage II colon cancer receiving adjuvant chemotherapy with tegafur-uracil.
• Identify predictive factors of chemosensitivity to this regimen in these patients.

OUTLINE: Available tumor tissue samples are analyzed by real-time reverse transcriptase-PCR for TS, DPD, TP, OPRT, VEGF, cyclooxygenase-2, and FPGS; by PCR for microsatellite instability and genomic deletions on chromosome arm 18q; and pathologically for tumor budding, Crohn's-like lymphoid reaction, category of extent of poor differentiation, and fibrotic cancer stroma. The candidate prognostic and predictive markers are analyzed for correlation with disease-free survival, relapse-free survival, and overall survival of patients.

• Study Type: Observational
• Enrollment (Actual): 1111

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan, 260-8717
    • Chiba Cancer Center
  • Fukuoka, Japan, 810-0065
    • National Hospital Organization Kyushu Medical Center
  • Gifu, Japan, 501-6062
    • Matsunami General Hospital
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital
  • Ibaraki, Japan, 311-3193
    • National Hospital Organization Mito Medical Center
  • Kagoshima, Japan, 892-8512
    • Nanpuh Hospital
  • Kanagawa, Japan, 228-8555
    • Kitasato University School of Medicine
  • Kumamoto, Japan, 861-8520
    • Japanese Red Cross Kumamoto Hospital
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Faculty of Medical and Pharmaceutical Sciences
  • Kyoto, Japan, 602-0841
    • Kyoto Prefectural University of Medicine
  • Kyoto, Japan, 602
    • Nishijin Hospital
  • Nagano, Japan, 380-0
    • Nagano Red Cross Hospital
  • Nagasaki, Japan, 852-8501
    • Nagasaki University Hospital
  • Nara, Japan, 6308145
    • Saiseikai Nara Hospital
  • Niigata, Japan, 950-1104
    • Saiseikai Niigata Daini Hospital
  • Okayama, Japan, 700-8558
    • Okayama University Medical School
  • Osaka, Japan, 543-8555
    • Osaka Red Cross Hospital
  • Osaka, Japan, 530-8480
    • Kitano Hospital
  • Osaka, Japan, 532-0
    • Osaka City Juso Hospital
  • Osaka, Japan, 540-0008
    • Otemae Hospital
  • Osaka, Japan, 546-0012
    • Higashi Sumiyoshi Morimoto Hospital
  • Osaka, Japan, 550-0012
    • Nissay Hospital
  • Osaka, Japan
    • Minamiosaka Hospital
  • Osaka, Japan, Joto-ku
    • Osaka Saiseikai Noe Hospital
  • Saitama, Japan, 330-0074
    • Saitama Social Insurance Hospital
  • Shizuoka, Japan, 420 -8630
    • Shizuoka City Hospital
  • Shizuoka, Japan, 424-0911
    • Shizuoka Municipal Shimizu Hospital
  • Tokyo, Japan, 162-8655
    • International Medical Center of Japan
  • Tokyo, Japan, 113-8603
    • Nippon Medical School
  • Tokyo, Japan, 108-8329
    • Mita Hospital at the International University of Health and Welfare
  • Tokyo, Japan, 143-8541
    • Toho University School of Medicine
  • Tokyo, Japan, 150-8935
    • Japanese Red Cross Medical Center
  • Tokyo, Japan, 173-8605
    • Teikyo University School of Medicine
  • Tokyo, Japan
    • Takasago Kyoritsu Hospital
  • Tokyo, Japan, 113-8510
    • Tokyo Medical and Dental University
  • Tokyo, Japan, 174-8691
    • Itabashi Chuo Medical Center
  • Yamagata, Japan, 990-2292
    • Yamagata Prefectural Central Hospital
  • Yamagata, Japan, 990-9585
    • Yamagata University Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 454-8502
      • Nagoya Ekisaikai Hospital
    • Nagoya, Aichi, Japan, 454-8509
      • Ban Buntane Houtokukai Hospital
    • Nagoya, Aichi, Japan, 466-8550
      • Nagoya University Hospital
    • Nagoya, Aichi, Japan, 466
      • Nagoya University School of Medicine
    • Nagoya, Aichi, Japan
      • Nagoya Midori Municipal Hospital
    • Okazaki, Aichi, Japan
      • Aichi Prefectural Hospital
  • Akita
    • Noshiro, Akita, Japan, 016-0014
      • Yamamoto Kumiai General Hospital
    • Yokote, Akita, Japan, 013-8610
      • Hiraka General Hospital
  • Chiba
    • Ichihara, Chiba, Japan, 299-0111
      • Teikyo University Chiba Medical Center
    • Inba-gunn, Chiba, Japan, 270-1694
      • Asahi General Hospital
  • Fukui
    • Fukui-shi, Fukui, Japan, 918-8503
      • Fukuiken Saiseikai Hospital
    • Yoshida-gun, Fukui, Japan, 910-1193
      • University of Fukui Hospital
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 812-8582
      • Kyushu University Hospital
    • Kitakyushu, Fukuoka, Japan, 802-0077
      • Kitakyushu Municipal Medical Center
    • Kurume, Fukuoka, Japan, 830-0011
      • Kurume University School of Medicine
    • Kurume, Fukuoka, Japan, 830-8543
      • Saint Mary's Hospital
    • Tagawa, Fukuoka, Japan, 826-8585
      • Social Insurance Tagawa Hospital
  • Fukushima
    • Fukushima-shi, Fukushima, Japan, 960-1295
      • Fukushima Medical University Hospital
  • Gifu
    • Gifu-shi, Gifu, Japan, 500-8323
      • Gifu Municipal Hospital
    • Hashima, Gifu, Japan, 501-6206
      • Hashima City Hospital
    • Ogaki-shi, Gifu, Japan, 503-8502
      • Ogaki Municipal Hospital
  • Gunma
    • Maebashi-shi, Gunma, Japan, 371-8511
      • Gunma University Graduate School of Medicine
    • Otashi, Gunma, Japan, 373-8550
      • Gunma Cancer Center
  • Hiroshima
    • Fukuyama, Hiroshima, Japan, 720-0825
      • National Hospital Organization Fukuyama Medical Center
    • Fukuyama, Hiroshima, Japan, 721-8581
      • Chugoku Central Hospital of the Mutual Aid Association of Public School Teachers
    • Kure, Hiroshima, Japan, 737-0023
      • National Hospital Organization Kure Medical Center
    • Miyoshi, Hiroshima, Japan, 728-8502
      • Miyoshi Central Hospital
  • Hokkaido
    • Asahikawa, Hokkaido, Japan, 078-8510
      • Asahikawa Medical College
    • Asahikawa, Hokkaido, Japan, 078-8510
      • Otaru Ekisaikai Hospital
    • Hakodate, Hokkaido, Japan, 040-8611
      • Hakodate Goryoukaku Hospital
    • Otaru-shi, Hokkaido, Japan, 047-0031
      • Hirosaki University, School of Medicine
    • Sapporo, Hokkaido, Japan, 060-8604
      • Sapporo City General Hospital
    • Sapporo, Hokkaido, Japan, 060-8556
      • Sapporo Medical University
    • Sapporo, Hokkaido, Japan, 060-8638
      • Hokkaido University Graduate School of Medicine
  • Hyogo
    • Akashi, Hyogo, Japan, 673-8558
      • Hyogo Cancer Center
    • Akou, Hyogo, Japan, 678-0232
      • Ako City Hospital
    • Amagasaki, Hyogo, Japan, 660-8511
      • Kansai Rosai Hospital
    • Amagasaki, Hyogo, Japan, 660-0828
      • Hyogo Prefectural Amagasaki Hospital
    • Himeji, Hyogo, Japan, 672-8501
      • Himeji Central Hospital
    • Himeji, Hyogo, Japan, 670-0801
      • Himeji St. Mary's Hospital
    • Kakogawa, Hyogo, Japan, 675-8611
      • Kakogawa Municipal Hospital
    • Kobe, Hyogo, Japan, 650-0017
      • Kobe University Hospital
    • Kobe, Hyogo, Japan, 651-2273
      • Nishi-Kobe Medical Center
    • Kobe, Hyogo, Japan, 653-0013
      • Kobe West City Hospital
    • Kobe, Hyogo, Japan, 654-0155
      • Kobe Medical Center
    • Kobe, Hyogo, Japan, 655-0031
      • Sano Hospital
    • Kobe-shi, Hyogo, Japan, 650-0046
      • Kobe City General Hospital
    • Nishinomiya, Hyogo, Japan, 663-8501
      • Hyogo College of Medicine
    • Sumoto, Hyogo, Japan, 656-0013
      • Hyogo Prefectural Awaji Hospital
    • Takarazuka, Hyogo, Japan, 665-0827
      • Takarazuka Municipal Hospital
    • Takarazukai, Hyogo, Japan, 665-0873
      • Higashi Takarazuka Satoh Hospital
  • Kagawa
    • Miki, Kagawa, Japan, 761-0793
      • Kagawa University Hospital
    • Takamatsu, Kagawa, Japan, 760-8557
      • Kagawa Prefectural Central Hospital
  • Kanagawa
    • Ashigarakami-gun, Kanagawa, Japan, 258-0003
      • Kanagawa Prefectural Ashigawa-kami Hospital
    • Chigasaki, 253-0083, Kanagawa, Japan, 253-0083
      • Chigasaki Municipal Hospital
    • Kawasaki, Kanagawa, Japan, 211-8510
      • Kanto Rosai Hospital
    • Yokohama, Kanagawa, Japan, 241-0815
      • Kanagawa Cancer Center
    • Yokohama, Kanagawa, Japan, 245-0006
      • International Goodwill Hospital
    • Yokohama, Kanagawa, Japan, 240
      • Yokohama City Hospital
  • Kochi
    • Nankoku, Kochi, Japan, 783-8505
      • Kochi Medical School
  • Kumamoto
    • Uki, Kumamoto, Japan, 869-0
      • National Hospital Organization - Kumamotominami Hospital
    • Yatsushiro, Kumamoto, Japan, 866-8660
      • Yatsushiro Health Insurance General Hospital
  • Kyoto
    • Kanigyou-ku, Kyoto, Japan, 602-8026
      • Kyoto Second Red Cross Hospital
  • Mie
    • Thu-shi, Mie, Japan, 514-8507
      • Mie University Graduate School of Medicine
  • Miyagi
    • Natori-shi, Miyagi, Japan, 981-1293
      • Miyagi Cancer Center
    • Sendai, Miyagi, Japan, 981-0911
      • Tohoku Rosai Hospital
  • Nagano
    • Iida, Nagano, Japan, 395-8502
      • Iida Municipal Hospital
    • Komagane, Nagano, Japan, 399-4191
      • Showa-Inan General Hospital
    • Matsumoto, Nagano, Japan, 390-8510
      • Aizawa Hospital
    • Nagano-shi, Nagano, Japan, 381-8551
      • Nagano Municipal Hospital
    • Nakano, Nagano, Japan, 383-0021
      • Hokushin Hospital
  • Nara
    • Yamatotakada, Nara, Japan, 635-0022
      • Kenseikai Nara Coloproctology Center
  • Niigata
    • Niigata-shi, Niigata, Japan, 951-8566
      • Niigata Cancer Center Hospital
    • Niigata-shi, Niigata, Japan, 951-8122
      • Niigata University Medical and Dental Hospital
  • Oita
    • Yufu-shi, Oita, Japan, 879-5593
      • Oita University Hospital
  • Okayama
    • Kurashiki, Okayama, Japan, 710-8602
      • Kurashiki Central Hospital
  • Osaka
    • Hirakata, Osaka, Japan, 573-8511
      • Hoshigaoka Koseinenkin Hospital
    • Izumisano, Osaka, Japan, 598-8577
      • Rinku General Medical Center
    • Mino, Osaka, Japan, 562-0014
      • Minoh City Hospital
    • Osaka-shi, Osaka, Japan, 534-0021
      • Osaka City General Hospital
    • Osaka-shi, Osaka, Japan, 543-8502
      • Osaka Police Hospital
    • Osaka-shi, Osaka, Japan, 553-0003
      • Osaka Kosei Nenkin Hospital
    • Osaka-shi, Osaka, Japan, 558-8558
      • Osaka General Medical Center
    • Sakai-shi, Osaka, Japan, 591-8025
      • Osaka Rosai Hospital
    • Suita-shi, Osaka, Japan, 564-0082
      • Suita Municipal Hospital
    • Takatsuki, Osaka, Japan, 569-8686
      • Osaka Medical College
    • Tondabayashi, Osaka, Japan, 584-0082
      • Saiseikai tondabayashi Hospital
  • Saitama
    • Fukaya, Saitama, Japan, 366-0052
      • Fukaya Red Cross Hospital
    • Hasuda, Saitama, Japan, 349-0123
      • Hasuda Hospital
    • Kawagoe-shi, Saitama, Japan, 350-8550
      • Saitama Medical School Hospital
    • Tokorozawa, Saitama, Japan, 359-8513
      • National Defense Medical College
  • Shiga
    • Nagahama, Shiga, Japan, 526-8580
      • Nagahama City Hospital
    • Otsu, Shiga, Japan, 520-0804
      • Otsu Municipal Hospital
  • Shimane
    • Izumo-shi, Shimane, Japan, 693-0068
      • Shimane Prefectural Central Hospital
  • Shizuoka
    • Fujieda, Shizuoka, Japan, 426-8677
      • Fujieda Municipal General Hospital
    • Hamamatsu-shi, Shizuoka, Japan, 431-3192
      • Hamamatsu University School of Medicine
    • Yaizu, Shizuoka, Japan, 425-8505
      • Yaizu Municipal Hospital
  • Tochigi
    • Shimotsuke-shi, Tochigi, Japan, 329-0498
      • Jichi Medical School
    • Utsunomiya, Tochigi, Japan, 320-0834
      • Tochigi Cancer Center
  • Tokushima
    • Anan, Tokushima, Japan, 770-8503
      • Anan Kyoei Hospital
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-8560
      • St. Luke's International Hospital
    • Fuchu, Tokyo, Japan, 183-8524
      • Tokyo Metropolitan Fuchu Hospital
    • Kodaira, Tokyo, Japan, 187-0004
      • Shouwa General Hospital
    • Komae, Tokyo, Japan, 201
      • Daisan Hospital
    • Mitaka, Tokyo, Japan, 181-8611
      • Kyorin University School of Medicine - Mitaka Campus
    • Shinjuku-ku, Tokyo, Japan, 169-0073
      • Social Insurance Chuo General Hospital
    • Shinjyuku-ku, Tokyo, Japan, 162-8666
      • Tokyo Women's Medical University
  • Tottori
    • Yonago, Tottori, Japan, 683-8503
      • Tottori University - Faculty of Medicine
  • Toyama
    • Takaoka-shi, Toyama, Japan, 933-8555
      • Koseiren Takaoka Hospital
  • Wakayama
    • Tanabe, Wakayama, Japan, 646-8588
      • Social Insurance Kinan Hospital
  • Yamaguchi
    • Shimonoseki, Yamaguchi, Japan, 750-0061
      • Shimonoseki Kosei Hospital
    • Shimonoseki, Yamaguchi, Japan, 240-8555
      • National Hospital Organization - Kanmon Medical Center
    • Ube, Yamaguchi, Japan, 755-8505
      • Yamaguchi University Graduate School of Medicine
  • Yamanashi
    • Chu-o-shi, Yamanashi, Japan, 409-3898
      • University of Yamanashi Faculty of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with curatively resected stage II colon cancer in Japan.

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the colon or rectosigmoid

  • Stage II disease
• Must be registered on clinical trial TMDU-BRI-CC-05-01
• Must have resected tumor tissue available
• No hereditary colorectal cancer

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1

PRIOR CONCURRENT THERAPY:

• Not specified

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
UFT adjuvant therapy group; UFT is given at a dose of 500-600 mg/day as tegafur in 2 divided doses after meals for 5 days, followed by a 2-day rest. This one-week cycle is repeated for one year. During protocol treatment, clinical findings and laboratory values are evaluated every month. After the completion of protocol treatment, patients are followed-up, according to the schedule defined in the study protocol, for 5 years until recurrence, other malignancy or death is confirmed.	Drug: UFT adjuvant chemotherapy; UFT is given at a dose of 500-600 mg/day as tegafur in 2 divided doses after meals for 5 days, followed by a 2-day rest. This one-week cycle is repeated for one year.; Other Names: Adjuvant chemotherapy with tegafur-uracil
Observation group; Patients are followed-up without adjuvant treatment, according to the schedule defined in the study protocol, for 5 years until recurrence, other malignancy or death is confirmed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mRNA levels	mRNA levels of patients are analyzed by the Danenberg tumor profile (DTP) method in the following indicators: thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), orotate phosphoribosyltransferase (OPRT), folylpolyglutamate synthetase (FPGS) vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (Cox-2) mRNA levels.	9years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of microsatellite instability (MSI) and chromosomal instability (CIN)	MSI and CIN (i.e., 18q LOH) are analyzed using paraffin embedded samples.	At enrollment
Histopathological examination	Tumor budding, category of extent of poor differentiation, Crohn's-like lymphoid reaction, and fibrotic cancer stroma are analyzed using hematoxylin and eosin (H&E) staining of paraffin embedded samples.	At enrollment

Collaborators and Investigators

• Sponsor: Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
• Collaborators: Tokyo Medical and Dental University
• Investigators: Study Chair: Kenichi Sugihara, MD, PhD, Tokyo Medical and Dental University

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: May 9, 2009
• First Submitted That Met QC Criteria: May 9, 2009
• First Posted (Estimate): May 12, 2009

Study Record Updates

• Last Update Posted (Estimate): September 28, 2016
• Last Update Submitted That Met QC Criteria: September 26, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; adenocarcinoma of the colon; stage II rectal cancer; stage II colon cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tegafur
• Other Study ID Numbers: CDR0000551714; TMDU-BRI-CC-05-02