2000). In addition, the combination of Herceptin with vinorelbine has recently been studied (Burstein et al. 2001). In this study, 30 of 40 women treated with Herceptin (4 mg/kg x 1, 2 mg/kg weekly thereafter) and vinorelbine (25 mg/m2 weekly, with dose adjusted each week for neutrophil count) responded to therapy, for an overall response rate of 75% (95% confidence interval 57% to 89%). Neutropenia was the only grade IV toxicity. No patients had symptomatic heart failure. Grade 2 cardiotoxicity was observed in 3 patients; prior cumulative doxorubicin dose in excess of 240 mg/m2 and borderline pre-existing cardiac function were associated with this toxicity. 1.4 SAFETY Experience with Herceptin administration has shown that the drug is relatively safe. The most significant safety signal observed during clinical trials was cardiac dysfunction (principally clinically significant congestive heart failure [CHF]), particularly when Herceptin was given in combination with an anthracycline-containing regimen. Much of the cardiac dysfunction was reversible on discontinuation of Herceptin. In addition, during the first infusion with Herceptin, a symptom complex most commonly consisting of fever and/or chills was observed in approximately 40% of patients. The symptoms were usually mild to moderate in severity and controlled with acetaminophen, diphenhydramine, or meperidine. These symptoms were uncommon with subsequent infusions. However, in the post-approval setting, more severe adverse reactions to Herceptin have been reported. These have been categorized as hypersensitivity reactions (including anaphylaxis), infusion reactions, and pulmonary events. Rarely, these severe reactions culminated in a fatal outcome.