SWOG-S9635 Fluorouracil Plus Ethynyluracil in Advanced Colorectal Cancer Not Responded to Fluorouracil

OBJECTIVES: I. Assess the confirmed response rate to fluorouracil (5-FU) plus ethynyluracil (776C85) in patients with metastatic colorectal cancer that has been demonstrated to be resistant to 5-FU. II. Assess time to progression and survival in this group of patients. III. Assess the frequency and severity of toxicities associated with this treatment.

OUTLINE: Patients are stratified according to relapse while receiving adjuvant therapy (relapse within 12 months of completing adjuvant therapy vs relapse while receiving adjuvant therapy). Patients receive oral doses of ethynyluracil (776C85) and fluorouracil twice daily for 28 days followed by 1 week of rest. Treatment continues every 5 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months the first year, every 4 months the second year, and every 6 months thereafter.

PROJECTED ACCRUAL: A total of 35-75 patients will be accrued for this study.

• Histologically or cytologically proven metastatic colorectal cancer
• Prior surgery required
• No prior treatment for metastatic disease
• Disease progression while on fluorouracil adjuvant therapy
• Bidimensionally measurable disease
• Age: Over 18
• Performance status: SWOG 0-2
• Hematopoietic: Platelet count at least 100,000/mm3, Absolute granulocyte count at least 1,500/mm3
• Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT or SGPT no greater than 3 times ULN (no greater than 5 times ULN if liver involvement)
• Renal: Creatinine clearance at least 50 mL/min
• Other: Must be able to swallow and retain oral medications No nutritional support by gastrostomy feeding tube or parenteral support No intractable vomiting or nausea
• Patients with history of prior malignancy must be currently disease free and off all therapy for that malignancy
• Not pregnant or nursing Fertile patients must use effective contraception
• Biologic therapy: No concurrent immunotherapy Chemotherapy; At least 3 weeks since prior chemotherapy and recovered; No concurrent flucytosine; No other concurrent chemotherapy
• Endocrine therapy: No concurrent hormonal therapy
• Radiotherapy: Prior adjuvant pelvic radiation or radiation to one area of recurrence allowed At least 4 weeks since prior radiotherapy and recovered Total area of bone marrow irradiation must not exceed 25% No concurrent radiotherapy
• Surgery: At least 2 weeks since prior surgery for colorectal cancer and recovered No prior resection of the stomach or small intestine
• Other: No other concurrent anticancer therapy