Background: Numerous preclinical and clinical trials showed that circadian-modified 5-fluoro-2-deoxyuridine (floxuridine; FUdR) infusion administered with a totally implantable programmable pump is associated with lower toxicity, higher dose intensity, and improved therapeutic outcome in renal cell carcinoma (RCC).
Methods: Between July 1988 and March 1991, the authors treated 30 patients with metastatic RCC with circadian-timed infusion FUdR at 0.15 mg/kg/day x 14 days at monthly intervals with a programmable portable pump. Time modification was simplified with one-third of the daily dose given between 11 p.m. and 11 a.m. and two-thirds given between 11 a.m. and 11 p.m. The characteristics of the patients were as follows: 19 men; 11 women; median age, 60 years (range, 28-82 years); median World Health Organization (WHO) performance status: 2 (range: 0-3); 77% failed prior systemic treatment. The main sites of tumor involvement were lungs (70%) and bone (53%).
Results: One hundred twenty-eight cycles were completed (median, 3 cycles per patient; range: 1-18 cycles per patient). Toxicity developed in 10 (33%) patients, primarily Grade 1-2 nausea/vomiting (6 patients), Grade 3 diarrhea (3 patients), and Grade 2 hand-foot syndrome (1 patient). In 28 patients evaluable for response, the authors observed four partial responses (14%; 95% confidence interval, 4-33%) and five stabilizations of the disease, including three minor responses. The median duration of response was 12 months (range, 8-24 months), and the median survival time was 6 months.
Conclusion: Circadian continuous infusion FUdR may be an effective outpatient treatment for metastatic RCC, with low toxicity and good quality of life in responding patients.