Trials of new combinations of Herceptin in metastatic breast cancer.

Herceptin extends survival in human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer patients when administered with paclitaxel or anthracycline/cyclophosphamide (AC), and the combination with 3-weekly paclitaxel is the current standard first-line therapy. However, other combinations may be equally effective. This review provides information on recent and ongoing trials of new Herceptin combinations. Preliminary results indicate that Herceptin plus epirubicin/cyclophosphamide may be effective without the cardiotoxicity of the AC combination. Weekly paclitaxel plus Herceptin has produced responses in 83% of HER2-positive patients treated. Co-administering Herceptin with other cytotoxic agents has also been investigated, with combination partners being chosen based on in vitro synergy with Herceptin, known efficacy as monotherapy and convenience of weekly administration (e.g. docetaxel, vinorelbine). High response rates have been observed in these clinical trials, e.g. up to 80% in combination with vinorelbine. Furthermore, Herceptin in combination with weekly paclitaxel, docetaxel or vinorelbine was well tolerated: there was no significant cardiotoxicity or unexpected toxicity and the combination showed an adverse event profile similar to that seen with monotherapy with the cytotoxic agent. Thus, Herceptin produces additional clinical benefit when added to all the cytotoxic agents with which it has been examined, further demonstrating its potential for use in HER2-positive breast cancer patients.