Trastuzumab infusion-related reactions

Trastuzumab 4 mg/kg IV over 90 minutes on day 1 followed by 2 mg/kg over 90 minutes (30 minutes if no infusion-related reactions) once weekly or 8 mg/kg IV over 90 minutes on day 1 followed by 6 mg/kg IV over 90 minutes every 3 weeks Infusion reactions (fever, chills, rigors), nausea, vomiting, pain at tumor sites, headaches, dizziness, dyspnea, hypotension, heart failure... 

Docetaxel should be administered the day after trastuzumab for the first cycle because of the potential for infusion-related reactions to trastuzumab, particularly during or after the first administration. Serious adverse reactions to trastuzumab infusion that have been reported infrequently include dyspnoea (shortness of breath), hypotension, wheezing, hypertension, bronchospasm, supraventricular tachyarrhythmia, reduced oxygen saturation, anaphylaxis, respiratory distress and urticaria (itching). The majority of these events occur during or within 2.5 hours of the start of the first infusion. Should an infusion reaction occur, the infusion should be discontinued and the patient monitored until resolution of any observed symptoms - the infusion may be resumed when symptoms abate. If the first cycle is well tolerated then dosing of the drugs in future cycles may occur on the same day. 

Trastuzumab also may cause infusion-related or hypersensitivity reactions (particularly with the first infusion). However, a more concerning possible side effect is cardiac dysfunction (including CHF). Although patients may develop cardiac dysfunction with trastuzumab alone, the incidence is significantly increased in patients who receive trastuzumab in combination with paclitaxel or in those patients with previous use of anthracyclines. 

Toxicities included an infusion reaction consisting of fever, chills, pain, asthenia, nausea, and vomiting. This syndrome was typically observed after the initial infusion, was self-limited, and frequently did not recur with subsequent infusions. The most serious toxicity was cardiac dysfunction, defined as clinical findings of congestive heart failure and/or subclinical declines in cardiac ejection fraction, which was seen in 5% of patients. Cardiotoxicity was unanticipated, as it had not been detected in previous studies. The mechanism for this effect is unclear, but is likely related to trastuzumab s antiproferative effect on HER2-mediated homeostasis and response to injury. 

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