title: Weekly continuous infusion of 5-fluorouracil with oral leucovorin in metastatic breast cancer patients with primary resistance to doxorubicin.
abstract: Doxorubicin-resistant metastatic breast cancer (MBC) is a very poor prognosis scenario, where only taxanes have shown activity, often at the expense of severe toxicity that compromises palliation. This study was undertaken to test the antitumor activity and tolerability of infusional 5-fluorouracil (5-FU) modulated with low-dose oral leucovorin (LV), in heavily pretreated patients with stringent criteria of primary resistance to doxorubicin, visceral involvement, and suboptimal performance status. Twenty-six patients with measurable MBC and primary resistance to anthracyclines received a weekly outpatient 48-hour infusion of high-dose 5-FU with low dose oral leucovorin. All patients were assessable for response and toxicity. Eight partial responses were seen (30% response rate) in soft tissue and visceral sites, with a median response duration of eight months (5 + to 12). 98% of the cycles were minimally toxic or non-toxic. Toxicities included mucositis, diarrhea, and plantar-palmar-syndrome. Our results suggest that this schedule of LV-modulated infusional 5-FU can produce a substantial number of long-lasting responses and meaningful palliation to this very poor prognosis population.
authors.affiliation: Oncology Department, Hospital Universitario San Carlos, Madrid, Spain. yxnieto@entente.uhcolorado.edu
authors.forename: Y
authors.initials: Y
authors.lastname: Nieto
authors.forename: M
authors.initials: M
authors.lastname: Martín
authors.forename: J L
authors.initials: JL
authors.lastname: Alonso
authors.forename: A
authors.initials: A
authors.lastname: Casado
authors.forename: F
authors.initials: F
authors.lastname: Ayala
authors.forename: J A
authors.initials: JA
authors.lastname: López-Martín
authors.forename: A
authors.initials: A
authors.lastname: Rodríguez-Lescure
authors.forename: E
authors.initials: E
authors.lastname: Díaz-Rubio
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008875:Middle Aged; D010166:Palliative Care; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D004317:Doxorubicin; D002955:Leucovorin; D005472:Fluorouracil