title: Phase 1 combination study of eribulin mesylate with trastuzumab for advanced or recurrent human epidermal growth factor receptor 2 positive breast cancer.
abstract: Eribulin mesylate (Halaven®) is a novel inhibitor of microtubule dynamics that has demonstrated a survival benefit in patients with locally recurrent or metastatic breast cancer who previously received at least two chemotherapeutic regimens including an anthracycline and a taxane. Although trastuzumab is indicated for patients with human epidermal growth factor receptor 2 positive (HER2+) breast cancer, a phase 1 study to evaluate tolerability/safety of eribulin mesylate with trastuzumab has not been conducted. Therefore, a study of eribulin mesylate in combination with trastuzumab was conducted to evaluate dose limiting toxicity (DLT), tolerability/safety, pharmacokinetics (PK), and efficacy and to estimate the recommended dose in Japanese patients with advanced or recurrent HER2+ breast cancer. Eribulin mesylate (1.4 mg/m(2)) was administered on days 1 and 8 of every 3 week cycle. Trastuzumab was administered with a 4 mg/kg loading dose followed by 2 mg/kg weekly doses or with an 8 mg/kg loading dose followed by 6 mg/kg tri-weekly doses. A total of 12 patients (six for each regimen) received eribulin mesylate and trastuzumab. No DLT was observed and the recommended dose of eribulin mesylate in combination with trastuzumab was estimated as 1.4 mg/m(2). Common adverse events were neutropenia, leukopenia, anaemia and alopecia. This combination therapy was well tolerated and the neutropenia observed was manageable. No PK drug-drug interaction between eribulin and trastuzumab was observed. Since a transient ejection fraction decreased was observed in two patients, cardiac function should be routinely assessed in patients receiving the combination therapy of eribulin mesylate with trastuzumab (ClinicalTrials.gov Identifier: NCT01432886).
authors.affiliation: Department of Breast and Medical Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan, hrmukai@east.ncc.go.jp.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Mukai
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saeki
authors.forename: Ken
authors.initials: K
authors.lastname: Shimada
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Naito
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Matsubara
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Obaishi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Namiki
authors.forename: Yasutsuna
authors.initials: Y
authors.lastname: Sasaki
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005663:Furans / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007659:Ketones / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases; D013318:Stroke Volume / Q000187:drug effects; D000068878:Trastuzumab; D016896:Treatment Outcome; D000095662:Polyether Polyketides
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005663:Furans; D007659:Ketones; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C490954:eribulin; D000095662:Polyether Polyketides