PRELIMINARY RESULTS OF PHASE I COMBINATION STUDY OF ERIBULIN MESYLATE WITH TRASTUZUMAB IN PATIENTS WITH HUMAN EPIDERMAL GROWTH FACTOR 2 (HER2) POSITIVE ADVANCED OR METASTATIC BREAST CANCER

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Abstract

Eribulin mesylate (eribulin), a novel microtubule-targeted inhibitor, was approved ‘inoperable or recurrent breast cancer’ on April 2011 in Japan. In therapeutic system, trastuzumab is used for patients with HER2-positive breast cancer but the safety of combination of eribulin with trastuzumab is not established. And so, we conducted the clinical phase I study of eribulin in combination with trastuzumab in patients with HER2-positive breast cancer to evaluate dose limiting toxicity (DLT), and investigate tolerability and safety. Six patients with prior chemotherapy including trastuzumab and taxanes for advanced or metastatic breast cancer were evaluated in DLT evaluation periods (for 21 or 28 days after drug administration). Eribulin (1.4 mg/m2) was administered as an IV bolus on days 1 and 8 every 3-week cycle, which is approved dosage and schedule, and trastuzumab was administered as an IV infusion weekly (method A). As a result, no adverse events corresponding to DLT were observed, and the common adverse events were neutropenia and leukopenia. On day 15 after drug administration, one of six patients showed the slight decrease in left ventricular ejection fraction, but it was recovered on day 22. And thus, the combination of eribulin with trastuzumab was tolerable in DLT evaluation periods, and the safety profile in this study was similar to that in the past clinical studies of eribulin monotherapy. On the other hand, since the acute cardiac failure was observed, it was thought that the assessment of cardiac function in the combination of eribulin with trastuzumab should be carried out carefully.

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