• Christos Christodoulou, Ioannis Kostopoulos, Haralabos P Kalofonos, Evangelos Lianos, Mattheos Bobos, Evangelos Briasoulis, Helen Gogas, Evangelia Razis, Dimosthenis V Skarlos, George Fountzilas, and Study of the Hellenic Cooperative Oncology Group.
• Second Department of Medical Oncology, Henry Dunant Hospital, Athens, Greece.
• Oncology. 2009 Jan 1; 76 (4): 275-85.

ObjectiveCombination 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.MethodsPatients 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.ResultsAmong 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.ConclusionTrastuzumab combined with PLD every 3 weeks is feasible, effective and safe in HER2-positive patients.Copyright 2009 S. Karger AG, Basel.

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