Pilot Study of Oral Eniluracil/5-FU in the Palliation of Hormone-Refractory Prostate Cancer

Objectives: Chemotherapy has an established role in the palliative therapy of patients with hormone-refractory prostate cancer (HRPC). However, optimal chemotherapy for HRPC remains poorly defined. This pilot study examined the activity and toxicity of oral 5-fluorouracil (5-FU) in combination with eniluracil for the treatment of patients with HRPC. Materials and Methods: Eighteen patients with HRPC and painful bone metastases were enrolled, although 1 patient was deemed ineligible because of incidental gastric cancer. The median age was 69 years (range, 57–82 years), median Eastern Cooperative Oncology Group performance status was 1 (range, 0–2) and median prostate specific antigen (PSA) level was 146 μg/l (range 4–2020 μg/l). Eniluracil (10 mg/m2) and 5-FU (1 mg/m2) were given orally, twice daily, for 28 days in 35-day cycles. Results: Two patients (11%) had partial pain responses (95% confidence interval, 0–29%), and 6 patients (35%) had stable pain for a minimum of 8 weeks. A reduction in analgesic use occurred in four patients (23%), and five patients (29%) experienced stable analgesic use. A partial PSA response (>50% reduction on at least two occasions, 5 weeks apart) was achieved in three patients (18%), and eight patients (48%) had stable PSA responses (PSA was rising pretreatment). Grade 4 diarrhea occurred in one patient. Grade 3 toxicities were as follows: anemia, 1 patient; lethargy, 1 patient; and deterioration in liver function, 1 patient. Conclusions: Oral eniluracil/5-FU is well tolerated in this patient population but has only modest activity. Studies in combination with other active agents may be warranted in patients with HRPC.