title: Trastuzumab and vinorelbine as first-line therapy for HER2-overexpressing metastatic breast cancer: multicenter phase II and pharmacokinetic study in Japan.
abstract: Tolerability and response rate to weekly combination chemotherapy with trastuzumab and vinorelbine in Japanese women with HER2-overexpressing breast cancer not previously receiving either therapy were assessed. Tumor response was evaluated every 4 weeks and adverse events were graded. A total of 23 patients from six participating centers in Japan were enrolled. Median dose intensity of vinorelbine was 16.9 mg/m2/week and response rate was 73% (complete response+partial response); complete response=9%, partial response=64%, and progressive disease=5%. Time to progression was 361 days, with 75.0% of liver metastases and 60% of lung metastases responding to this treatment. The most common adverse events were leukocytopenia and neutropenia (96%); however, hematologic toxicity associated with vinorelbine was manageable by adjusting the dose. No pharmacokinetic differences for vinorelbine were found between single administration and combination with trastuzumab. This combination therapy produced high response rates and good tolerability, indicating a promising role in first-line chemotherapy for HER2-overexpressing metastatic breast cancer in Japan.
authors.affiliation: Division of Medical Oncology, The Cancer Institute Ariake Hospital of Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo 135-8550, Japan. nahomi.tokudome@jfcr.or.jp
authors.forename: Nahomi
authors.initials: N
authors.lastname: Tokudome
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hatake
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
authors.forename: Muneaki
authors.initials: M
authors.lastname: Sano
authors.forename: Hiroji
authors.initials: H
authors.lastname: Iwata
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sato
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saeki
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Aogi
authors.forename: Shigemitsu
authors.initials: S
authors.lastname: Takashima
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D000068878:Trastuzumab; D016277:Ventricular Function, Left / Q000187:drug effects; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000077235:Vinorelbine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D014747:Vinblastine; D000077235:Vinorelbine