Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop
growing or die. Combining more than one drug may kill more tumor cells. It is not yet known
which chemotherapy regimen is more effective for stage III colon cancer. Randomized phase
III trial to compare the effectiveness of fluorouracil plus leucovorin with or without
irinotecan in treating patients who have undergone surgery for stage III colon cancer.
I. Compare the overall and disease free survival of patients with stage III colon cancer
treated with adjuvant fluorouracil and leucovorin calcium with or without irinotecan.
II. Assess prognostic markers and correlate their expression with disease free and overall
survival of these patients.
III. Assess the influence of diet, body mass index, and physical activity on the risk of
cancer recurrence and survival in these patients.
IV. Assess the influence of diet, obesity, and physical activity on the risk of toxicity
associated with adjuvant therapy in these patients.
V. Determine whether pathological features (including tumor grade, tumor mitotic
(proliferation) index, tumor border configuration, and host lymphoid response to tumor; and
lymphatic vessel, venous vessel and perineural invasion) predict outcome in this patient
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to lymph
node involvement (1-3 vs 4 or more), histology (poorly differentiated or undifferentiated vs
well or moderately differentiated), and preoperative serum CEA (less than 5.0 ng/mL vs at
least 5.0 ng/mL vs unknown). Study therapy must begin within 21-56 days after surgery.
Patients are randomized to one of two treatment arms:
ARM I: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV beginning 1
hour into leucovorin calcium infusion weekly for 6 weeks. Treatment is repeated every 8
weeks for 4 courses.
ARM II: Patients receive irinotecan IV over 90 minutes, followed by leucovorin calcium IV,
then followed by fluorouracil IV weekly for 4 weeks. Treatment is repeated every 6 weeks for
Patients complete a food questionnaire at the beginning of the third course and then at 6
months after study therapy.
Patients are followed every 3 months for 2 years, every 4 months for 2 years, then annually
PROJECTED ACCRUAL: A total of 1260 patients will be accrued for this study within 3 years.
- Patients must have histologically documented adenocarcinoma of the colon; the gross
inferior (caudad) margin of the primary tumor must lie above the peritoneal
reflection; tumor must have been completely resected, including negative radial
- There must be no history of distant metastatic disease at the time of registration
- Pathological evaluation must show Modified Astler-Coller stage C (TxN1-2M0) disease
- No previous or concurrent malignancy is allowed except for adequately treated basal
cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which
the patient has been disease-free for five years
- Zubrod performance status of 0-2
- Non-pregnant and not nursing, as chemotherapy is thought to present substantial risk
to the fetus/infant; men and women of reproductive potential may not participate
unless they have agreed to use an effective contraceptive method while in this study
- Granulocytes >= 1,500/ul
- Platelet count >= 100,000/ul
- Creatinine =< 1.5 x upper limits of normal
- Bilirubin =< upper limit of normal