10742 Background: HER2 over-expression was found to be an independent prognostic predictor of overall survival and time to relapse in breast cancer patients. Trastuzumab binds to the extracellular domain of HER2 cell receptor, thereby inhibiting the growth of breast cancer cells that over-express HER2. Objective: examine safety and toxicity profile of trastuzumab prolonged treatment (> 6 months) in heavily pre-treated HER2+ metastatic breast cancer patients. Methods: Between February 1999 and April 2005, 20 patients received weekly standard trastuzumab infusion until disease progression or serious adverse events. Population characteristics: median age: 46.6 years (30–65 years), ER+: 47.6%, PR+: 42.8%. Previous treatment: hormonotherapy: 12 patients (60%), two or more lines: 5 patients: (41.6%). All patients received previous chemotherapy: one line: 7 patients (35%), two lines: 10 (50%), three or more lines:3 (15%). Median trastuzumab treatment time was 11 months (6–36 months) Trastuzumab was administered as monotherapy in 5 patients (25%) and in combination in 15 patients (75%): 60% with docetaxel, 26.6% with paclitaxel, and 13.3 % with gemcitabine or vinorelbine Safety was primary trial end point, hence pre-treatment cardiac (baseline LVEF ≥55% by Echo or MUGA scan) and liver function assessment were required; and then, repeated each two months. Results: As regards cardiac adverse events, 2 patients (10%) receiving also docetaxel, developed supraventricular tachycardia reversible with 1 week treatment arrest. After 17 months, trastuzumab was discontinued in one of these two patients due to asymptomatic decrease in LVEF to 35 % (baseline LVEF:65%). An increase in transaninases (per 3ULN) was noted in one patient (5%) after 12 months of treatment. Liver function normalized after two weeks trastuzumab interruption. Allergic phenomena, as hot flashes or chills during first infusion was described in 3 patients (15%). In combination therapy, asthenia (20%), nausea (10%), anemia (10%), foot and hand syndrome (5%) and myalgia (5%) were observed. Conclusions: Prolonged tratuzumab administration in heavily pre-treated patients seems to be a safe approach with predictable profile and reversible toxicity with trastuzumab discontinuance and standard medical care. No significant financial relationships to disclose.
A Multi-Center Trial to Evaluate the Safety and Toxicity of Nanoxel®-M in Breast Cancer Patients
