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Prospective Phase II Randomized Trial of Postoperative Adjuvant Chemotherapy in Patients With High Risk Colon Cancer

Phase 2
18 Years
70 Years
Open (Enrolling)
Colonic Diseases, Adenocarcinoma

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Trial Information

Prospective Phase II Randomized Trial of Postoperative Adjuvant Chemotherapy in Patients With High Risk Colon Cancer

Approximately 75% of all patients with colon carcinoma present at a stage when all gross
tumor can be surgically resected. Despite that high resectability rate, about 50% of all
colon adenocarcinoma patients die of subsequent metastatic disease not apparent at surgery.
These individuals could benefit from adjuvant local or systemic chemotherapy.

Based on the encouraging antitumor activity of 5-FU plus leucovorin(LV) in patients with
metastatic colon carcinoma6,7, several investigators reported their results using this
combination in the adjuvant setting. Results of an NSABP C-038 suggested that postoperative
5-FU plus leucovorin reduces the risk of colon cancer recurrence by 30% and the associated
mortality by 32% compared with MOF(semustine, vincristine, and 5-FU). Recently,
investigators from the IMPACT group9 analyzed the role of adjuvant 5-FU plus high dose
leucovorin given 5 days every 28 days for a total of six courses versus no treatment in
patients with stage II or III colon cancer. The treatment arm showed a significant reduction
(by 22%) in mortality (P=0.029) and a 35% reduction in relapse rate (P=0.0001). Preliminary
results from other studies have also suggested benefits of 5-FU plus leucovorin as adjuvant
treatment of colon cancer10,11,12. Those studies had employed chemotherapy with 5-FU plus
leucovorin, although there were differences in duration of treatment and drug dose among
those trials, it is striking that all revealed a similar magnitude of benefit for adjuvant
chemotherapy with 5-FU and leucovorin in node positive patients. At the present time, both
5-FU plus levamisole and 5-FU plus leucovorin can be considered acceptable adjuvant
chemotherapy regimens for patients with node positive disease.

Thymidylate synthase(TS) is a critical therapeutic target for the fluoropyrimidine cytotoxic
drugs that are the mainstay of the treatment for patients with advanced colorectal cancer.
TS provide the sole de nono source of thymidylate for DNA synthesis. The clinical importance
of TS in determining fluoropyrimidine cytotoxicity has been established in both clinical and
preclinical study. Increased expression of TS protein due to underlying gene amplification
has been described in cell lines selected for drug resistance by exposure to 5-FU.22,23
Several investigators have also demonstrated that intratumoral TS activity are predictive
for response to 5-FU.24-26 High TS activity was associated with no response, whereas a low
TS activity was associated with good response to 5-FU.

Inclusion Criteria:

Signed written informed consent. Curative resection of colon cancer and upper rectal
cancer, which is not planned for radiotherapy. Histologically proved adenocarcinoma of the
colon. Stages: T1-4N2M0 (LN ≧4) Age less or equal to 70 years old. Performance status: 0
to 1 (ECOG) Adequate liver function (Bil. < 2 mg/dl, GOT, GPT< 3x normal limit) Adequate
renal function (Cr < 2.0 mg/dl) Adequate bone marrow function(WBC ≧3500/mm3, Platelet
≧100000/mm3) Individual regular follow-up possible. 3.320 Patient who can receive adjuvant
chemotherapy within 6 weeks after operation.

Patient who can receive a "indwelling catheter" surgery.

Exclusion Criteria:

Uncontrolled intercurrent illness, e.g. active infection or concurrent major systemic
disease (e.g. psychosis, ESRD, heart failure [NYHA class III], liver cirrhosis [Child
B&C], or AIDS). Intestinal obstruction or occlusion postoperation. Pregnant or lactating
woman. Allergy to 5-Fluorouracil or leucovorin. Other primary cancer except skin squamous
or basal cell carcinoma or cured in-situ cancer of the cervix.

Previous treatment of chemotherapy or radiotherapy.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To compare the DFS and OS of HDFL vs. weekly bolus 5-FU plus high dose LV as adjuvant chemotherapy for N2 colon cancer

Principal Investigator

Cheng-Yi Wang, PHD

Investigator Role:

Study Chair

Investigator Affiliation:

Chang Gung Memorial Hospital


Taiwan: Department of Health

Study ID:




Start Date:

April 2002

Completion Date:

October 2012

Related Keywords:

  • Colonic Diseases
  • Adenocarcinoma
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Colonic Neoplasms
  • Colonic Diseases