Trastuzumab combined with pegylated liposomal doxorubicin in patients with metastatic breast cancer. phase II Study of the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation.
Title | Trastuzumab combined with pegylated liposomal doxorubicin in patients with metastatic breast cancer. phase II Study of the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Christodoulou, C., Kostopoulos I., Kalofonos H. P., Lianos E., Bobos M., Briasoulis E., Gogas H., Razis E., Skarlos D. V., & Fountzilas G. |
Corporate Authors | Study of the Hellenic Cooperative Oncology Group |
Journal | Oncology |
Volume | 76 |
Issue | 4 |
Pagination | 275-85 |
Date Published | 2009 |
ISSN | 1423-0232 |
Keywords | Adult, Aged, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Doxorubicin, Humans, Middle Aged, Polyethylene Glycols, Protein Kinases, PTEN Phosphohydrolase, Receptor, ErbB-2, TOR Serine-Threonine Kinases, Ventricular Function, Left |
Abstract | OBJECTIVE: Combination of trastuzumab and anthracyclines in metastatic breast cancer (MBC) is precluded due to cardiotoxicity. Pegylated liposomal doxorubicin (PLD) is the least cardiotoxic among the anthracyclines. We performed a phase II study of trastuzumab and PLD with biomarker evaluation.METHODS: Patients with MBC and HER2 overexpression, assessed as 3+ at local laboratories, received trastuzumab 8 mg/kg as loading dose followed by 6 mg/kg in combination with PLD 30 mg/m(2), both given every 3 weeks. To be eligible, patients should have received first-line chemotherapy for MBC or should have relapsed within a year of adjuvant taxane. Tumor tissue blocks were collected for central review and exploratory biomarker evaluation. Left-ventricular ejection fraction (LVEF) was closely monitored by cardiac ultrasound.RESULTS: Among 37 patients, an overall response rate of 22% was observed with a progression-free survival (PFS) of 6.5 months (0.8-31.1, 95% CI 2.7-10.3) and a survival of 18.7 months (1.6-40.8, 95% CI 3.7-33.7). No decline in LVEF was noticed. Overexpression of mTOR and TOP2A gene alterations were associated with better PFS. PTEN gene deletion was associated with resistance to treatment.CONCLUSION: Trastuzumab combined with PLD every 3 weeks is feasible, effective and safe in HER2-positive patients. |
DOI | 10.1159/000207504 |
Alternate Journal | Oncology |
PubMed ID | 19262067 |