• Incidence of NCI CTC grade 2-4 diarrhea during the first cycle (6 weeks) of CPT-11/5-FU/LV chemotherapy
  

• Severity of all grades of diarrhea, overall and by cycle
  
• Duration of diarrhea, by cycle
  
• Diarrhea grade, by day, by cycle
  
• Stool count, by day, by cycle
  
• Severity of asthenia (fatigue), by week.
  
• Asthenia will be assessed with the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) scale.
  
• Duration of asthenia, by week, as measured by the FACIT-Fatigue scale
  
• Type, frequency, severity, timing, and relatedness of all adverse events CPT-11/5-FU/LV treatment administration as characterized by median, mean, and range of doses given; dose modifications, omissions, and delays; and actual and relative dose intensity
  
• Compliance with celecoxib use Incidence, quantity, and duration of loperamide use
  
• Tumor response rate (overall and confirmed)using the World Health Organization [WHO] Response Evaluation Criteria in Solid Tumors [RECIST 2000]
  
• Serum tumor marker (carcinoembryonic antigen [CEA]) response rate (as characterized by a 50% reduction from baseline)
  
• Time to tumor progression (TTP)
  
• Time to treatment failure (TTF)
  
• Survival Post-study anticancer treatment
  
• Peak plasma levels and AUC 0-24 values for CPT-11 and its major metabolites, SN-38, SN-38 glucuronide (SN-38G), and aminopentane carboxylic acid (APC)
  
• Inflammatory cytokines which may serve as biomarkers for cancer-related outcomes Beta-glucuronidase as a potential biomarker for tumor response
  
• Health resource utilization (collected data to be evaluated separately from this protocol)
  

Inclusion Criteria:

• Diagnosis of colorectal cancer (either newly diagnosed or recurrent disease) with evidence of metastatic disease and present or past histological documentation of adenocarcinoma of the colon or rectum.
• Tumor must be measureable.
• Resolution of all acute toxic effects of any prior radiotherapy or surgical procedure.
• ECOG performance status 0 or 1. Age >= 18 years.
• Required baseline laboratory.
• Negative pregnancy test.
• Willingness and ability to comply with the treatment plan.

Exclusion Criteria:

• Current enrollment in another clinical trial.
• Prior adjuvant therapy for colorectal cancer <= 6 months prior to randomization.
• Prior systemic anticancer therapy or intra-arterial cytotoxic chemotherapy given as treatment for metastatic colorectal cancer.
• Known allergy to CPT-11, 5-FU, LV, celecoxib, other COX-2 inhibitors, non-steroidal anti-inflammatory drugs (NSAIDS), salicylates, or sulfonamides.
• Chronic concomitant use of full-dose aspirin, other NSAIDs or other COX-2 inhibitors for a chronic nonmalignant condition.
• A requirement for chronic concomitant use of low-dose (cardioprotective) aspirin.
• Chronic oral steroid use for treatment of a non-malignant condition.
• Known ulceration of the gastric or duodenal mucosa <= 30 days prior to randomization.
• Need for concomitant fluconazole or lithium.
• Any known significant bleeding disorder.
• Active inflammatory bowel disease or chronic diarrhea.