title: A phase II trial of vinflunine as monotherapy or in combination with trastuzumab as first-line treatment of metastatic breast cancer.
abstract: We investigated the microtubulin inhibitor vinflunine—with trastuzumab in human epidermal growth factor receptor-2 (HER2)-positive patients—as first-line metastatic breast cancer therapy. HER2-negative patients received vinflunine on day 1; HER2-positive patients received vinflunine/trastuzumab every 21 days. Forty-eight patients in each treatment group were planned; the sponsor terminated the study early. Thirty-two evaluable patients (vinflunine, 11; vinflunine/trastuzumab, 21) were enrolled. In HER2-positive patients, vinflunine/trastuzumab produced an objective response rate (33%), clinical benefit rate (71%), and progression-free survival (6.2 months). Grade-3/4 neutropenia occurred in 14 (44%) patients; gastrointestinal toxicities were common and six patients were hospitalized for treatment-related toxicity. The vinflunine/trastuzumab combination was active and well tolerated, but our results do not suggest advantages over taxane/trastuzumab or vinorelbine/trastuzumab.
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennesee, USA.
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
authors.forename: Michael
authors.initials: M
authors.lastname: McCleod
authors.forename: Fred
authors.initials: F
authors.lastname: Schreiber
authors.forename: Patrick
authors.initials: P
authors.lastname: Murphy
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Patton
authors.forename: Dana S
authors.initials: DS
authors.lastname: Thompson
authors.forename: Mythili
authors.initials: M
authors.lastname: Shastry
authors.forename: Mark
authors.initials: M
authors.lastname: Rubin
authors.forename: Marianne
authors.initials: M
authors.lastname: Melnik
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D010146:Pain / Q000139:chemically induced; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000068878:Trastuzumab; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D014747:Vinblastine; C111217:vinflunine