Combination Chemotherapy in Treating Patients With Colon Cancer
Combination Chemotherapy in Treating Patients With Colon Cancer
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
 they stop growing or die. It is not yet known which schedule of chemotherapy is most
 effective in treating colon cancer.

 PURPOSE: Randomized phase III trial to compare different schedules of chemotherapy using
 carboplatin with fluorouracil and leucovorin in treating patients who have stage IIB or stage
 III colon cancer.
OBJECTIVES:

 -  Compare the disease-free survival of patients with completely resected stage IIB or III
 colon cancer treated with adjuvant chronomodulated vs standard schedule fluorouracil and
 leucovorin calcium with or without carboplatin.

 -  Compare the overall survival of patients treated with these regimens.

 -  Compare the toxicity of these regimens in these patients.

 -  Compare the quality of life of patients treated with these regimens.

 -  Determine the dose intensities of fluorouracil and carboplatin in these patients.

 OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
 participating center and disease stage (IIB vs III). Patients are randomized to 1 of 4
 treatment arms.

 -  Arm I (standard schedule): Patients receive fluorouracil (5-FU) IV continuously and
 leucovorin calcium (CF) IV on days 1 and 2.

 -  Arm II (standard + carboplatin schedule): Patients receive 5-FU and CF as in arm I plus
 carboplatin IV on day 1.

 -  Arm III (chronomodulated schedule): Patients receive 5-FU IV continuously and CF IV
 continuously on days 1-4.

 -  Arm IV (chronomodulated + carboplatin schedule): Patients receive 5-FU and CF as in arm
 III plus carboplatin IV continuously on days 1-4.

 Quality of life is assessed.

 Treatment in all arms repeats every 14 days for up to 9 courses in the absence of disease
 progression or unacceptable toxicity.

 PROJECTED ACCRUAL: A total of 660-800 patients will be accrued for this study.
DISEASE CHARACTERISTICS:

 -  Histologically confirmed adenocarcinoma of the colon

 -  Stage IIB or III (Dukes stage B2 or C)

 -  Complete curative resection performed within the past 7 weeks (negative margins)

 -  No local or regional relapsed disease

 -  Tumor more than 15 cm above the anal margin

 -  Carcinoembryonic antigen less than 5 ng/mL (after surgery)

 -  No rectal cancer

 -  No metastatic disease

 PATIENT CHARACTERISTICS:

 Age

 -  18 and over

 Performance status

 -  ECOG 0-1 OR

 -  Karnofsky 60-100%

 Life expectancy

 -  Not specified

 Hematopoietic

 -  Neutrophil count at least 2,000/mm3

 -  Platelet count at least 100,000/mm3

 Hepatic

 -  Bilirubin no greater than 1.5 times upper limit of normal (ULN)

 -  SGOT and SGPT no greater than 5 times ULN

 Renal

 -  Creatinine no greater than 1.5 times ULN

 Cardiovascular

 -  No serious coronary disease

 Other

 -  Not pregnant

 -  Fertile patients must use effective contraception

 -  No concurrent infectious disease

 -  No other malignancy except adequately treated basal cell skin cancer or carcinoma in
 situ of the cervix

 PRIOR CONCURRENT THERAPY:

 Biologic therapy

 -  No prior immunotherapy

 Chemotherapy

 -  No prior chemotherapy

 Endocrine therapy

 -  Not specified

 Radiotherapy

 -  No prior radiotherapy (before or after surgery)

 Surgery

 -  See Disease Characteristics

 Other

 -  No concurrent participation in another clinical trial