title: Vinflunine: a new active drug for second-line treatment of advanced breast cancer. Results of a phase II and pharmacokinetic study in patients progressing after first-line anthracycline/taxane-based chemotherapy.
abstract: To evaluate the single agent activity, pharmacokinetics and tolerability of the novel tubulin targeted agent vinflunine (VFL) (320 mg m(-2) q 21 days) as second-line chemotherapy in patients with metastatic breast carcinoma (MBC). All patients had disease progression after anthracycline/taxane (A/T) therapy. They could have received a nonanthracycline adjuvant treatment and subsequently received a first-line A/T combination for advanced/metastatic disease; or relapsed >6 months after completion of adjuvant A/T therapy and were subsequently treated with the alternative agent; or relapsed within 6 months from an adjuvant A/T combination. Objective response was documented in 18 of 60 patients enrolled (RR: 30% (95% confidence interval (CI): 18.9-43.2%)). Among the responders, seven patients had relapsed during a period of <3 months from taxane-based regimen yielding a RR of 33.3%. The median duration of response was 4.8 months (95% CI: 4.2-7.2), median progression-free survival was 3.7 months (95% CI: 2.8-4.2) and median overall survival was 14.3 months (95% CI: 9.2-19.6). The most frequent adverse event was neutropenia (grade 3 in 28.3% and grade 4 in 36.7% of patients). No febrile neutropenia was observed. Fatigue (grade 3 in 16.7% of patients) and constipation (grade 3 in 11.7% of patients) were also common; these were non-cumulative and manageable permitting achievement of a good relative dose intensity of 93.5%. Vinflunine is an active agent with acceptable tolerance in the management of MBC patients previously treated with (A/T)-based regimens. These encouraging phase II results warrant further investigation of this novel agent in combination with other active agents in this setting or in earlier stages of disease.
authors.affiliation: Centre René Gauducheau, 44805 Saint Herblain, France.
authors.forename: M
authors.initials: M
authors.lastname: Campone
authors.forename: H
authors.initials: H
authors.lastname: Cortes-Funes
authors.forename: D
authors.initials: D
authors.lastname: Vorobiof
authors.forename: M
authors.initials: M
authors.lastname: Martin
authors.forename: C F
authors.initials: CF
authors.lastname: Slabber
authors.forename: E
authors.initials: E
authors.lastname: Ciruelos
authors.forename: E
authors.initials: E
authors.lastname: Bourbouloux
authors.forename: C
authors.initials: C
authors.lastname: Mendiola
authors.forename: F M
authors.initials: FM
authors.lastname: Delgado
authors.forename: C
authors.initials: C
authors.lastname: Colin
authors.forename: V
authors.initials: V
authors.lastname: Aslanis
authors.forename: P
authors.initials: P
authors.lastname: Fumoleau
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D003248:Constipation / Q000139:chemically induced; D018450:Disease Progression; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D018943:Anthracyclines; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane; C111217:vinflunine; D014747:Vinblastine