Ipilimumab (Yervoy), a new monoclonal antibody, has been approved by the Food and Drug Administration (FDA) for the treatment of late-stage (metastatic) melanoma. It's the first drug approved by the agency that has been shown to prolong life in patients with this dangerous skin cancer.
According to the FDA's news release regarding the approval, ipilimumab "blocks a molecule known as cytotoxic T-lymphocyte antigen" or CTLA-4, which "may play a role in slowing down or turning off the body's immune system, affecting its ability to fight off cancerous cells." Scientists believe the drug may allow the patient's immune system to "recognize, target, and attack cells in melanoma tumors."
The drug is administered intravenously, 3 mg/kg over 90 minutes every three weeks, for a total of four doses. The most common adverse effects are fatigue, diarrhea, pruritus, rash, and colitis. Serious and potentially life-threatening adverse effects are also possible. A black box warning states that ipilimumab can result in severe and even fatal immune-mediated adverse reactions resulting from T cell activation and proliferation. These immune-mediated reactions may involve any organ system; in clinical trials the most common of these were enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), and endocrinopathy. Although the majority of severe reactions occurred during infusion of the drug, some occurred weeks or months after treatment was discontinued.
The drug's label (http://1.usa.gov/hJU3Hi) warns that "patients may present with fatigue, headache, mental status changes, abdominal pain, unusual bowel habits, and hypotension or nonspecific symptoms" that may be thought to have other etiologies and that "unless an alternate etiology has been identified," such signs or symptoms should be considered to be immune mediated.
Because of its potential for serious adverse effects, ipilimumab was approved on the conditions that a "risk evaluation and mitigation strategy" (REMS) and a patient medication guide would be developed. The REMS consists of a communication plan to inform clinicians of the serious risks associated with this drug and to facilitate early identification of these reactions, as well as an overview of recommended management of patients with moderate or more severe immune-mediated adverse reactions. The medication guide should be dispensed with each dose given to provide patients and their caregivers with information about these serious adverse effects.
Assessment considerations. According to the drug's label, clinicians caring for patients who receive ipilimumab should assess patients for signs and symptoms of enterocolitis (fever, abdominal swelling, nausea, vomiting, diarrhea, rectal bleeding, and sluggishness), dermatitis (redness, itching, or blistering), neuropathy (motor damage: muscle weakness, cramps, muscle spasms, or a loss of balance and coordination; sensory damage: tingling, numbness, or pain; autonomic nerve damage: abnormal blood pressure and heart rate, diminished ability to perspire, constipation, bladder incontinence, and sexual dysfunction), and endocrinopathy (hypopituitarism, hypothyroidism, hyperthyroidism, adrenal insufficiency, Cushing's syndrome, and hypogonadism). Liver function, thyroid function, and clinical chemistry testing should be performed at baseline and then before each dose of ipilimumab, according to the instructions in the warning box. If adverse effects are severe, the drug should be permanently discontinued and high doses of IV steroids should be administered. For adverse effects that are moderate in severity, a dose should be withheld until there is improvement in or complete resolution of the immune-mediated adverse reaction; moderate doses of prednisone (less than 7.5 mg/day) or its equivalent should also be administered.
Nurses should encourage patients and their families to read the guide with each prescription (in this case each time the drug is to be administered intravenously) because it will contain the most up-to-date information about the drug's safety.