This multicenter, open-label phase I/II study was designed to determine the recommended dose, cardiac safety and antitumor activity of nonpegylated liposomal doxorubicin, paclitaxel and trastuzumab in patients with HER-2-overexpressing locally advanced nonoperable breast cancer (LABC) or metastatic breast cancer (MBC).
Sixty-nine adult patients from Spain participated, 15 in the dose escalating part and 54 at the recommended phase II dose. Women with measurable, previously untreated, HER-2-overexpressing LABC and MBC - and a baseline left ventricular ejection fraction (LVEF) > 50 percent - received weekly trastuzumab in combination with escalating doses of weekly paclitaxel and nonpegylated liposomal doxorubicin every three weeks for six cycles. Overall response rate was defined as the total of complete response plus partial response. LVEF was monitored every 3 weeks for the first 18 weeks and every eight weeks thereafter.
No case of symptomatic treatment-related cardiac failure was reported. A total of 12 patients (17%) developed asymptomatic minimal and reversible declines in LVEF. In eight of these patients, LVEF recovered to greater than or equal to 50% after a median time of nine weeks (range, 3-38 weeks). In the remaining patients, LVEF ranged from 44% to 49%.
The combination therapy was highly active and well-tolerated. The overall response rate, at the recommended phase II dose, was 98.1%: 29 patients achieved a complete response (53.7%) and 24 patients had a partial response (44.4%). This response rate ranks among the highest reported in HER-2-overexpressing breast cancer patients. The median time to progression was not reached in patients with locally advanced nonoperable breast cancer, while it exceeded 21 months in those with metastatic disease. The most common adverse events included alopecia (85.1%), mucosal inflammati
|SOURCE Sopherion Therapeutics, LLC|
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