Combination Chemotherapy in Treating Patients With 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