Low-dose continuous intravenous infusion of 5-fluorouracil for metastatic breast cancer

Abstract

Third-line chemotherapies for advanced breast cancer are difficult to tailor to the individual patient because of reduced tolerance and significant toxicity. Treatment with a continuous intravenous infusion of low-dose 5-fluorouracil (FU-LDCI) is generally well tolerated and thus, a reasonable option for heavily pretreated patients. From 1989 to 1995,106 consecutive patients with advanced breast cancer were treated with FU-LDCI. 5-Fluorouracil was given at an initial daily dose of 250 mg/m² administered continuously with the aid of an elastomer, non-electronic pump through a permanent central venous line for 21 days followed by a 7-day rest. The median age was 56 years (range, 30–82), the median ECOG Performance Status was 1 (range 0–4) and the median number of metastatic sites was 2 (range 1–4). Sixty-one percent of the patients had previously received more than 2 chemotherapy regimens which in 81% included adriamycin, and in 90% 5-fluorouracil. Eighty patients were evaluable for objective response: 17 of them had partial responses (21%, 95% CI: 14%–31%) and 23 stable disease (29%, 95% CI: 20%–40%). One-hundred five patients were evaluable for subjective response, with 46 reporting improvement (44%,95% CI: 35%–54%). Previous treatments with either 5-fluorouracil or adriamycin did not predict response to FU-LDCI. Median time to progression for patients with a partial response or stable disease was 259 days (range 82–737). The overall survival for the populations as a whole was 274 days (range 13–2264), and the median dose received was 1904 mg/week (range 753–4329). The main toxic effects were grades I and II mucositis, and nausea and vomiting (observed in 31% and 28%, respectively). Grade III toxicities were uncommon: mucositis in 3%, nausea and vomiting in 3%, anemia, thrombocytopenia and hepatitis in 2%, and skin toxicity (hand-foot syndrome) in 1%. Catheter-related thrombosis was observed in 2% of the patients, and there were no pump failures. A questionnaire concerning the impact of the treatment upon quality of life was completed by all of the 13 patients who were alive at the time of evaluation of the results, and all of them rated FU-LDCI as easy to tolerate. The monthly cost of FU-LDCI (USS1,051.00 in Switzerland) was lower than the cost of weekly low-dose adriamycin (USS1,483.00 in Switzerland), a treatment which is often used as a palliative regimen in similar circumstances. FU-LDCI is a useful, cost-effective third-line treatment for patients with metastatic breast cancer who need palliation with cytotoxic drugs.