Combination Chemotherapy in Treating Patients With Advanced or Metastatic Colorectal Cancer
Combination Chemotherapy in Treating Patients With Advanced or Metastatic Colorectal Cancer
RATIONALE: 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.

 PURPOSE: Randomized phase II trial to study the effectiveness of combination chemotherapy in
 treating patients who have advanced or metastatic colorectal cancer.
OBJECTIVES:

 -  Compare the efficacy of different schedules of irinotecan in combination with
 capecitabine as first-line therapy, in terms of objective response rate, in patients
 with advanced or metastatic colorectal cancer.

 -  Compare the time to treatment failure, time to progression, and overall survival of
 patients treated with these regimens.

 -  Compare the safety profile, in terms of toxicity, of these regimens in these patients.

 -  Determine the quality of life in patients treated with these regimens.

 OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
 performance status (0 vs 1); disease symptoms, including pain, weight loss, loss of appetite,
 malaise, and fever of unknown origin (yes vs no); weight loss during the past 6 months (more
 than 5% vs 5% or less); and disease-free interval (more than 6 months vs 6 months or less).
 Patients are randomized to 1 of 2 treatment arms.

 -  Arm I: Patients receive irinotecan IV over 1 hour on days 1, 8, 15, 22, and 29 and oral
 capecitabine twice daily on days 1-14 and 22-35.

 -  Arm II: Patients receive irinotecan IV over 1 hour on days 1 and 22 and oral
 capecitabine as in arm I.

 Treatment in both arms repeats every 6 weeks in the absence of disease progression or
 unacceptable toxicity.

 Quality of life is assessed at baseline, on day 1 of each course, and at the first visit
 after treatment failure.

 Patients are followed every 12 weeks for 1 year and then every 6 months thereafter.

 PROJECTED ACCRUAL: A total of 28-74 patients (14-37 per treatment arm) will be accrued for
 this study.
DISEASE CHARACTERISTICS:

 -  Histologically or cytologically confirmed advanced or metastatic colorectal cancer

 -  Unresectable disease

 -  At least 1 bidimensionally measurable lesion

 -  At least 2 cm in perpendicular diameters

 -  No evidence of CNS metastases

 PATIENT CHARACTERISTICS:

 Age:

 -  18 to 75

 Performance status:

 -  0-1

 Life expectancy:

 -  At least 3 months

 Hematopoietic:

 -  WBC at least 3,500/mm^3

 -  Platelet count at least 100,000/mm^3

 Hepatic:

 -  Bilirubin normal

 -  SGOT/SGPT no greater than 2.5 times upper limit of normal (ULN)

 -  Alkaline phosphatase no greater than 2.5 times ULN

 Renal:

 -  Creatinine no greater than 1.25 times ULN

 Cardiovascular:

 -  No clinically significant cardiac disease

 -  No congestive heart failure

 -  No New York Heart Association class III or IV heart disease

 -  No symptomatic coronary artery disease

 -  No uncontrolled cardiac arrhythmia

 -  No myocardial infarction within the past year

 Gastrointestinal:

 -  No evidence of dysphagia

 -  No malabsorption or intestinal obstruction that would affect absorption or excretion
 of study drugs

 -  No chronic diarrhea

 Other:

 -  No other malignancy within the past 5 years except adequately treated carcinoma in
 situ of the cervix or localized nonmelanoma skin cancer

 -  No psychiatric disability that would preclude study compliance

 -  No other significant medical condition

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception

 PRIOR CONCURRENT THERAPY:

 Biologic therapy:

 -  Not specified

 Chemotherapy:

 -  No prior chemotherapy for advanced or metastatic disease

 Endocrine therapy:

 -  Not specified

 Radiotherapy:

 -  Not specified

 Surgery:

 -  At least 4 weeks since prior major surgery to the gastrointestinal tract

 Other:

 -  No concurrent therapy for history of seizures or CNS disorder