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Phase III Trial Comparing a 28 Day Schedule of Daily Oral 5-FU Plus Eniluracil to Protracted Intravenous Infusion in Previously Untreated Patients With Advanced Colorectal Cancer

Phase 3
18 Years
Not Enrolling
Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum, Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IV Colon Cancer, Stage IV Rectal Cancer

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Trial Information

Phase III Trial Comparing a 28 Day Schedule of Daily Oral 5-FU Plus Eniluracil to Protracted Intravenous Infusion in Previously Untreated Patients With Advanced Colorectal Cancer


I. Compare the response rate, response duration, and survival of patients with advanced
colorectal cancer treated with oral fluorouracil (5-FU) and eniluracil or with protracted
infusion 5-FU.

II. Compare the toxicity of these treatment regimens in this patient population.

OUTLINE: This is a randomized study. Patients are stratified according to performance status
(0 vs 1-2) and measurable disease (yes vs no). Patients are randomized to one of two
treatment arms.

ARM I: Patients receive fluorouracil IV as a continuous infusion for 28 days.

ARM II: Patients receive eniluracil/fluorouracil orally twice a day for 28 days.

Treatment continues every 35 days in the absence of disease progression or unacceptable

Patients are followed at least every 10 weeks for 1 year.

Inclusion Criteria:

- Patients with measurable or nonmeasurable histologically confirmed adenocarcinoma of
the colon and rectum are eligible provided patient has metastatic, recurrent or
residual disease, and tumor is beyond hope of surgical eradication; all pre-study
scans documenting disease must be done =< 4 weeks prior to randomization

- Measurable tumor is defined as a known mass that can be clearly measured in two
dimensions by physical examination, CT scan, radionuclide liver scan, or on
chest x-ray by a ruler or calipers; the largest diameter of the lesion must
measure >= 2 cm by at least one method of evaluation

- Patients must have had no prior therapy for advanced disease

- Patients may have had prior adjuvant treatment with 5-FU provided that the last dose
was received > 12 months prior to entering the study; no prior chemotherapy other
than adjuvant 5-FU is allowed

- Patients with prior radiotherapy are acceptable, but patients should have measurable
or nonmeasurable disease outside the radiation port and/or progressive disease within
the previously radiated volume; in addition, it must be at least 2 weeks since
administration of radiation therapy and all signs of toxicity must have abated

- Bilirubin =< 1.5 x upper limit of normal (ULN)

- SGOT =< 3 x ULN

- Because Eniluracil changes the metabolism of 5-FU such that it is excreted primarily
by the kidneys, an estimated creatinine clearance calculated using the Cockcroft and
Gault formula must be obtained in patients with a serum creatinine > institutional
normal limits; the estimated creatinine clearance must be >= 50 ml/min prior to
starting treatment with Eniluracil/5-FU; if not, a measured creatinine clearance must
be done (using a 24 hour urine collection); the measured creatinine clearance must be
> 50 ml/min for the patient to be eligible

- Absolute neutrophil count >= 2000 mm³

- Platelet count >= 100,000 mm³

- ECOG performance status 0-2

- No evidence of significant active infection (e.g., pneumonia, peritonitis, wound
abscess, etc.) at time of study entry

- No evidence of serious intercurrent illness such as uncontrolled diabetes mellitus,
hypothyroidism, malabsorption syndrome or heart failure

- No prior neoplastic diseases (within 5 years) aside from the current malignancy or
curatively resected melanoma, skin cancer or cervical carcinoma in situ

- No treatment with folinic acid, interferon, flucytosine or topical 5-FU within the
previous 14 days

- Not pregnant or lactating; pregnant and lactating women are excluded from the study
because effects on the fetus are unknown and there may be a risk of increased fetal

- Women of childbearing potential and sexually active males are strongly advised to use
an accepted and effective method of contraception

Type of Study:


Study Design:

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

Outcome Measure:

Overall survival

Outcome Time Frame:

Up to 1 year

Safety Issue:


Principal Investigator

John Hines

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

April 1999

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Colon
  • Adenocarcinoma of the Rectum
  • Recurrent Colon Cancer
  • Recurrent Rectal Cancer
  • Stage IV Colon Cancer
  • Stage IV Rectal Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Colonic Neoplasms
  • Rectal Neoplasms
  • Colorectal Neoplasms



Eastern Cooperative Oncology Group Boston, Massachusetts  02215