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

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

The combination of docetaxel and trastuzumab was as effective as reported in other similar studies and was well tolerated in these patients.

• Authors: Nobuaki Sato, Muneaki Sano, Toshio Tabei, Taro Asaga, Jiro Ando, Hirofumi Fujii, Naohito Yamamoto, Masafumi Kurosumi, Kenichi Inoue, Morihiko Kimura
• Journal: Breast cancer (Tokyo, Japan) (Breast Cancer) Vol. 13 Issue 2 Pg. 166-71 ( 2006) ISSN: 1340-6868 [Print] Japan
• PMID: 16755112 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Taxoids
• Docetaxel
• Receptor, ErbB-2
• Trastuzumab

Topics

• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Bone Neoplasms (secondary)
• Breast Neoplasms (drug therapy, mortality, pathology)
• Docetaxel
• 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, mortality, pathology)
• Receptor, ErbB-2 (metabolism)
• Respiratory Tract Neoplasms (secondary)
• Risk Assessment
• Skin Neoplasms (secondary)
• Survival Analysis
• Taxoids (administration & dosage)
• Trastuzumab
• Treatment Outcome