Combination docetaxel and trastuzumab treatment for patients with HER-2-overexpressing metastatic breast cancer: a multicenter, phase-II study

• Published in: Breast cancer (Tokyo, Japan) Japan), 2006, Vol.13 (2), p.166-171
• Main Authors: Sato, Nobuaki, Sano, Muneaki, Tabei, Toshio, Asaga, Taro, Ando, Jiro, Fujii, Hirofumi, Yamamoto, Naohito, Kurosumi, Masafumi, Inoue, Kenichi, Kimura, Morihiko
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bone Neoplasms - secondary; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Hematologic Diseases - chemically induced; Humans; Liver Neoplasms - secondary; Lymphatic Metastasis; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Neoplasms, Hormone-Dependent - drug therapy; Neoplasms, Hormone-Dependent - mortality; Neoplasms, Hormone-Dependent - pathology; Receptor, ErbB-2 - metabolism; Respiratory Tract Neoplasms - secondary; Risk Assessment; Skin Neoplasms - secondary; Survival Analysis; Taxoids - administration & dosage; Trastuzumab; Treatment Outcome
• ISSN: 1340-6868; 1880-4233
• DOI: 10.2325/jbcs.13.166

Pre-clinical and clinical studies indicate that a combination of docetaxel and trastuzumab may effectively treat patients with human epidermal growth factor receptor-2 (HER-2) overexpressing metastatic breast cancer. We evaluated the efficacy and safety of this combination in a multicenter, open-label phase II study in Japan. Women with metastatic breast cancer whose tumors overexpressed HER-2, as assessed by immunohistochemistry and by fluorescence in situ hybridisation, received 2 to 6 cycles of docetaxel (70 mg/m2, every 3 weeks) and trastuzumab (4 mg/kg loading dose, 2 mg/kg weekly thereafter). The primary endpoint was tumor response. Secondary endpoints were time to disease progression and adverse events. Of the 40 women enrolled in the study, 27 (68%) completed 6 cycles of treatment. Three patients discontinued the study before the second cycle. Median follow-up was 20.8 months (range, 0.6 to 30.9 months). The overall response rate was 65% (26/40; 95% CI, 48% to 79%). The median time to progression was 6.8 months (range, 0.6 to 21.2 months). Of the 40 patients, 35 (88%) had grade 3 or 4 leukopenia, and 33 (83%) had grade 3 or 4 neutropenia. Most instances of leukopenia and neutropenia were manageable by reducing the dose of docetaxel or by treatment with granulocyte colony-stimulating factor. In 4 patients, left ventricular ejection fraction decreased by more than 10% from baseline. The combination of docetaxel and trastuzumab was as effective as reported in other similar studies and was well tolerated in these patients.