Phase I clinical trial of liposomal-encapsulated doxorubicin citrate and docetaxel, associated with trastuzumab, as neo-adjuvant treatment in stages II and IIIA, HER2-overexpressing breast cancer patients. GEICAM 2003-03 study.

BACKGROUND: We carried out a phase I clinical trial to establish the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of the combination of liposome-encapsulated doxorubicin citrate (LD) and docetaxel in breast cancer patients. PATIENTS AND METHODS: Patients with HER-2-overexpressing stages II and IIIA breast cancers were treated in different dose cohorts of three patients. The MTD cohort was expanded up to six patients. The patients received LD and docetaxel every 21 days, plus weekly trastuzumab, with pegfilgrastim support.
RESULTS: A total of 20 patients were enrolled, 18 of them being assessable for toxicity and response. DLTs observed for this combination were diarrhea, fatigue, febrile neutropenia, stomatitis, myalgia, and nonneutropenic infection (pneumonia). LD 50 mg/m(2) and docetaxel 60 mg/m(2) every 21 days have been the MTD, with no episode of DLT observed. Seven patients developed left ventricular ejection fraction decline (six grade 1 and one grade 2). No interruptions of the treatment were needed as a consequence of cardiac toxicity. Pathologic complete response was achieved in eight patients (44%).
CONCLUSIONS: The MTD and recommended dose for phase II trials of LD and docetaxel are 50 and 60 mg/m(2), respectively. The achieved results on cardiotoxicity are promising.