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. Copyright 2009 S. Karger AG, Basel.
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. Copyright 2009 S. Karger AG, Basel.
Authors: Susana M Campos; Suzanne T Berlin; Leroy M Parker; Wendy Y Chen; Craig A Bunnell; Tina Atkinson; Julie Lee; Ursula Matulonis; Michelle S Hirsch; Lyndsay Harris; Carolyn N Krasner Journal: Int J Clin Oncol Date: 2010-04-20 Impact factor: 3.402
Authors: Sandra M Swain; Sung-Bae Kim; Javier Cortés; Jungsil Ro; Vladimir Semiglazov; Mario Campone; Eva Ciruelos; Jean-Marc Ferrero; Andreas Schneeweiss; Adam Knott; Emma Clark; Graham Ross; Mark C Benyunes; José Baselga Journal: Lancet Oncol Date: 2013-04-18 Impact factor: 41.316
Authors: George Fountzilas; Christos Christodoulou; Mattheos Bobos; Vassiliki Kotoula; Anastasia G Eleftheraki; Ioannis Xanthakis; Anna Batistatou; George Pentheroudakis; Nikolaos Xiros; Irene Papaspirou; Anna Koumarianou; Pavlos Papakostas; Dimitrios Bafaloukos; Dimosthenis V Skarlos; Konstantine T Kalogeras Journal: J Transl Med Date: 2012-10-23 Impact factor: 5.531