title: 5-Fluorouracil rechallenge by protracted infusion in refractory breast cancer.
abstract: The authors assessed the value of protracted low-dose 5-fluorouracil (5-FU) infusion (250 mg/m2/day) in refractory breast cancer. Thirty-six patients with prior 5-FU exposure who were not eligible for other investigational therapeutic measures mainly due to extensive prior chemotherapy (median, four regimens) and poor performance status (median of 3, Zubrod scale) were enrolled. Thirty-four patients were evaluable for toxicity and 32 for response. Concurrent radiotherapy was given to 17 patients. The median duration of 5-FU treatment was 65 days (range, 19-508+) delivering a median cumulative 5-FU dose of 13.75 g/m2 (4.75-144.5+). The median number of interruptions of infusion was 1 (0-16) for a median of 7 days (1-25). One patient achieved complete remission, and four a partial response, for a median of 129 days (101-412) and a response rate of 16%. Five additional patients had a minor objective response (16%), whereas 15 (48%) had no change, and seven progressed (22%). The main toxicities seen were oral mucositis in 13 patients, hand-foot syndrome in six, Coombs'-positive hemolytic anemia in two, and progressive liver dysfunction in two patients who also had cirrhotic changes on computed tomography. Myelosuppression was uncommon and transient. Elective temporary interruptions of the 5-FU infusion diminished the incidence of mucocutaneous toxicity. Hemoglobin indices consistently displayed macrocytic features which did not readily revert to baseline after discontinuation of 5-FU infusion. Despite the adverse characteristics of the treated population, 5-FU infusion demonstrated moderate activity in refractory breast cancer with clinical resistance to prior 5-FU-containing regimens. Intermittent scheduled interruptions of infusion rendered this method of 5-FU delivery nontoxic.
authors.affiliation: Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
authors.forename: K
authors.initials: K
authors.lastname: Jabboury
authors.forename: F A
authors.initials: FA
authors.lastname: Holmes
authors.forename: G
authors.initials: G
authors.lastname: Hortobagyi
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009061:Mouth Mucosa / Q000187:drug effects; D010865:Pilot Projects; D013280:Stomatitis / Q000139:chemically induced
chemical_list: D005472:Fluorouracil