Herceptin Adjuvant Trials

An interaction of doxorubicin with the anti-HER2 receptor humanized monoclonal antibody, trastuzumab (Herceptin), has been reported. Most patients who received trastuzumab in early trials had been pretreated with anthracyclines. Despite this, preliminary information suggested that reduced systolic cardiac function was an adverse effect of trastuzumab (119). More recently, this problem has been further highlighted in a study of women with metastatic breast cancer (120). Patients who had not received prior anthracycline-containing adjuvant chemotherapy were at greater risk of cardiotoxicity when they received trastuzumab in combination with doxorubicin or cyclophosphamide (27 and 75% respectively), compared with only 11% of patients who received trastuzumab in combination with pachtaxel (120,121). The risk of cardiac events in patients treated with doxorubicin, cyclophosphamide, and trastuzumab increased markedly after a cumulative doxorubicin dose of 360 mg/m. This suggests synergistic cardiotoxicity with trastuzumab and doxorubicin. Trastuzumab is therefore currently licensed only for use in conjunction with pacli-taxel or docetaxel and not with conventional doxorubicin. 

A total of 469 patients were enrolled into a randomized, multicenter, phase III trial of chemotherapy with or without Herceptin [52]. All patients had previously untreated, IHC 2+/3+ MBC. Patients who had previously received anthracyclines in the adjuvant setting were randomized to receive paclitaxel (175 mg m 3-weekly) alone (n=96) or with Herceptin (n=92). All other patients were randomized to receive anthracycline (doxorubicin 60 mg m or epirubicin 75 mg m ) plus cyclophosphamide (600 mg m ) alone (n=138) or with Herceptin (n=143) (Fig. 5.7). The primary endpoint was TTP. Secondary endpoints were ORR, DR, TTF, OS and 1-year survival. An independent RFC determined disease progression and response. 

Two trials (NSABP B-31 and Intergroup N9831) conducted in North America were examining Herceptin with the standard US adjuvant regimen of AC followed by a taxane. The Breast Cancer International... 

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