An Infusion Reaction to Cetuximab

The patient, “DJ,” is a 53-year-old Hispanic male who sought medical attention for persistent fullness and discomfort in the right submandibular region. Imaging studies, which included a CT scan of the head and neck, revealed a 2-cm right tonsillar lesion, and lymph node involvement. A PET/CT scan showed intense hypermetabolic activity in the right tonsil, and a large necrotic right lymph node (level 2). No other areas of hypermetabolic activity were noted. A CT-guided biopsy of DJ’s right tonsillar lesion was performed, and the pathology was positive for squamous cell carcinoma.

The patient experienced a mild infusion reaction during a cetuximab infusion to treat his tonsillar tumor. Cetuximab was stopped and normal saline was infused. He was given oxygen via nasal cannula; acetaminophen (for his fever); and, to reduce his itching, rash, shortness-of-breath, and hypotension, he was given epinephrine, diphenhydramine, and hydrocortisone. Nurses need to document in the patient record when infusion reactions occur, how much drug was infused, the patient’s signs and symptoms, and the medications given to treat the reaction.

DJ was then referred to a head and neck surgeon, who decided that surgery would not be his best treatment option; therefore, DJ was then evaluated by both a medical and a radiation oncologist. The medical and radiation oncologists recommended that DJ receive concurrent treatment with the monoclonal antibody cetuximab (Erbitux) and radiation therapy. DJ is coming to the treatment center to begin his treatment regimen. He is to receive cetuximab at a loading dose of 400 mg/m2, followed by weekly cetuximab with daily radiation therapy for 7 weeks.

After the premedications are administered, the cetuximab infusion is started. DJ’s vital signs are stable, he has no complaints, and he feels well. Thirty minutes into the infusion, DJ calls the nurse. He is complaining of shortness-of-breath, itching, hives on his arms, nausea, and low back pain. In addition, he has a fever. The cetuximab infusion is stopped, and IV normal saline is infused. Assessment of DJ shows that he has a patent airway, no stridor, urticaria, and is hypotensive, but he is awake, alert, and answers questions appropriately. DJ is having a mild hypersensitivity reaction to the cetuximab. The nurse notifies DJ’s medical oncologist and initiates her institution’s hypersensitivity reaction protocol.

Cetuximab

Cetuximab is a chimeric (containing both human and mouse sequences) monoclonal antibody.[1] It is approved by the US Food and Drug Administration (FDA), in combination with radiation therapy, for treatment of squamous cell carcinoma of the head and neck, and for recurrent metastatic disease after treatment with a platinum-based therapy.[2]

Cetuximab also is FDA-approved for treatment of colorectal cancer, as monotherapy for patients with epidermal growth factor receptor (EGFR)-expressing disease who have failed to respond to treatment with both oxaliplatin (Eloxatin) and irinotecan (Camptosar)-containing regimens, and in combination with irinotecan for patients whose tumors express EGFR and which are refractory to irinotecan-based therapy.[2]

Infusion Reactions

The immune system is always involved in infusion reactions.[3] Some are allergic in nature and are mediated by immunoglobulin E (IgE); these are called anaphylactic reactions.[4] Anaphylactoid reactions represent the majority of infusion reactions.[5] Anaphylactoid reactions are not IgE-mediated, involve partial hypersensitivity, and tend to be less life-threatening than anaphylactic reactions.[5]

Cytokine release causes most of the infusion reactions related to monoclonal antibodies.[6,7] Cytokines, such as interleukin, interferon, and tumor necrosis factor, are released into circulation after destruction of a targeted cell by either phagocytosis or cytolysis; this occurs when immune-effector cells (monocytes, macrophages, cytotoxic T cells, natural killer cells) bind to the Fc (fragment, crystallizable) region (the constant portion) of the antibody and target the cell for death. This process is initiated when a monoclonal antibody binds with an antigen on the targeted cell.[6]

TABLE 1

Infusion-Related Toxicity

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