Three oral
5-fluorouracil (5-FU)
therapies have been approved by the US Food and Drug Administration or are in development for the treatment of patients with
breast cancer:
capecitabine, UFT, and 5-FU/
eniluracil.
Capecitabine has been approved for
breast cancer patients whose disease is
paclitaxel-resistant, and either
anthracycline-resistant or for whom further
anthracycline use is not indicated. A response rate of 20% was observed in an open-label phase II trial of
capecitabine in heavily pretreated patients with metastatic
breast cancer.
Diarrhea and
hand-foot syndrome were the most frequently reported toxicities. In a randomized phase II study of
capecitabine vs
paclitaxel in
breast cancer patients who had failed
anthracyclines, response rates were 36% for
capecitabine vs 21% for
paclitaxel. Several phase II trials of 5-FU/
eniluracil in
breast cancer are ongoing. Preliminary response data from one of these trials on 31 patients with
anthracycline- and
taxane-resistant advanced
breast cancer showed a 16% partial response rate. Grade 3-4 treatment-related toxicities included
diarrhea (8%),
nausea (3%), and
granulocytopenia (3%). In Japan, UFT is widely used for the treatment of
breast cancer in both the adjuvant and metastatic settings, though studies in the United States are just getting under way. A phase II trial conducted in Madrid, Spain evaluated the combination of UFT,
methotrexate, and
leucovorin as
salvage therapy for
breast cancer patients. The overall response rate was 38% among 21 patients, and
diarrhea was the most common toxicity. Many questions remain unanswered about the optimal use of oral
5-FU agents in
breast cancer. There seems little question that these agents have substantial activity and will find a place in the therapeutic armamentarium.