title: Effective treatment of advanced breast cancer with vinorelbine, 5-fluorouracil and l-leucovorin plus human granulocyte colony-stimulating factor.
abstract: A phase II trial was performed to investigate the efficacy and tolerance of vinorelbine (VNB), 5-fluorouracil (5-FU), l-leucovorin (LLV) and recombinant human granulocyte colony-stimulating factor (G-CSF) in advanced breast cancer. Between August 1994 and October 1996, 53 patients entered this trial. Thirty-seven patients were previously untreated and 16 patients had failed previous palliative chemotherapy with (n = 12) or without anthracyclines (n = 4). Therapy consisted of VNB 40 mg m(-2) diluted in 250 ml of saline infused over 30 min on days 1 and 14 and LLV 100 mg m(-2) administered by intravenous bolus injection and 5-FU 400 mg m(-2) diluted in 500 ml of saline infused over 2 h, both given on days 1-5 every 4 weeks. G-CSF was administered at 5 microg kg(-1) day(-1) subcutaneously on days 6-10 during each cycle. Treatment was continued in cases of response or stable disease until a total of six courses were completed. The overall response rate was 59% for chemotherapeutically naive patients (95% confidence interval 42-75%), including five complete responses (CR; 13%) and 17 partial responses (PR; 46%); ten patients (27%) had stable disease (SD) and only five (14%) progressed (PD). Second-line chemotherapy with this regimen resulted in 3/16 (19%) objective remissions, but nine patients had SD and four had PD. The median time to progression was 10.5 months (range 2-23) in previously untreated patients and 7.0 months (range 2-19) in those who had failed prior chemotherapy. After a median follow-up time of 14 months, 29 patients (55%) are still alive with metastatic disease; median survival has not been reached yet. The dose-limiting toxicity was myelosuppression: WHO grade III and IV neutropenia occurred in 15 (28%) and four patients (8%), and was complicated by septicaemia in two; grade III anaemia and thrombocytopenia were noted in four (8%) and three (6%) patients respectively. Severe (WHO grade 3) non-haematological toxicities included stomatitis in 6% and nausea/vomiting and alopecia in 2% each. Our data suggest that the combination of vinorelbine, 5-fluorouracil and l-leucovorin plus G-CSF is an effective first line regimen for treatment of advanced breast cancer. Overall toxicity was modest, with myelosuppression being the dose-limiting side-effect. Other severe adverse reactions were uncommon.
authors.affiliation: Department of Internal Medicine I, Vienna University Medical School, Austria.
authors.forename: G V
authors.initials: GV
authors.lastname: Kornek
authors.forename: K
authors.initials: K
authors.lastname: Haider
authors.forename: W
authors.initials: W
authors.lastname: Kwasny
authors.forename: F
authors.initials: F
authors.lastname: Lang
authors.forename: G
authors.initials: G
authors.lastname: Krauss
authors.forename: M
authors.initials: M
authors.lastname: Hejna
authors.forename: M
authors.initials: M
authors.lastname: Raderer
authors.forename: G
authors.initials: G
authors.lastname: Weinländer
authors.forename: D
authors.initials: D
authors.lastname: Depisch
authors.forename: W
authors.initials: W
authors.lastname: Scheithauer
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012074:Remission Induction; D016019:Survival Analysis; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D014747:Vinblastine; D002955:Leucovorin; D000077235:Vinorelbine; D005472:Fluorouracil