Simplified chronomodulated continuous infusion of floxuridine in patients with metastatic renal cell carcinoma.

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.