Clinical recommendations for the use of lapatinib ditosylate plus capecitabine for patients with advanced or metastatic HER2-positive breast cancer

Primary and acquired resistance to trastuzumab pose a therapeutic challenge when treating patients with HER2 (erbB-2)-positive locally advanced or metastatic breast cancer (MBC). The recent introduction of lapatinib (Tykerb/Tyverb, GlaxoSmithKline, Brentford, UK) provides a new management option for such patients. A prospective, randomized phase III clinical trial has confirmed that lapatinib in combination with capecitabine extends time to progressive disease in HER2-positive MBC, compared with capecitabine alone in patients with disease progression despite prior anthracycline, taxane and trastuzumab therapy. Preliminary data also indicate that lapatinib may exert a beneficial effect on brain metastases, a common sanctuary site for HER2-positive breast cancer following trastuzumab treatment. The tolerability of lapatinib is commensurate with that of other erbB family tyrosine kinase inhibitors and no significant new adverse events have emerged following its introduction into clinical practice. In particular, no additive cardiotoxicity has been observed when lapatinib is prescribed after trastuzumab therapy. Based on the published literature and supplemented by clinical experience, this article provides practical management recommendations for the use of lapatinib plus capecitabine in patients with MBC. Issues addressed include patient selection, baseline evaluation and monitoring for clinical benefit. The minimization and management of adverse events is also discussed in detail, particularly the dermatological and gastrointestinal effects, which are the most clinically significant side-effects of lapatinib therapy. Further recommendations cover the minimization of drug interactions, anticipated dosing alterations and the optimal employment of oral anticancer regimens.