Successful rapid desensitization to intravenous etoposide using a 14-step protocol

Abstract

Chemotherapeutic agents used for treating neoplastic disease have the potential to induce hypersensitivity reactions (HSRs). With an increase in the use of these drugs, the potential for HSRs has also increased and more cases are frequently being reported. According to Cernadas et al, drug hypersensitivity accounts for more than 15% of all adverse drug reactions, affecting more than 7% of the general population and 10% to 20% of all hospitalized patients. Because these reactions often require the discontinuation of first-line therapies to avoid a life-threatening situation, oncologists have been increasingly consulting allergists to assist in the management of these HSRs. Available options to solve the problem in the presence of HSRs include changing drugs, premedicating with antihistamines and corticosteroids, and/or desensitization. Unfortunately, prescribing an alternative medication is not always feasible especially in the case of targeted therapies, which demand the use of a specific drug. Although a premedication treatment can diminish or prevent the risk of HSRs, it is not sufficient by itself because these drugs often only mask early signs of HSRs rather than prevent them. Etoposide, an antimitotic epipodophyllotoxin active against numerous malignant conditions including germ cell neoplasms, lymphomas, and carcinomas is reported to induce HSRs in 6% of the patients. However, its incidence of anaphylaxis is 0.7%. Manifestations of HSRs to etoposide vary but tend to include bronchospasms, dyspnea, and hypotension. Multiple desensitization studies and case reports have suggested that HSRs to chemotherapeutic agents can be avoided with low infusion rates and managed with the use of pretreatments that include antihistamines and corticosteroids. We present a case in which a 79-year-old woman with limitedstage small cell lung carcinoma was admitted to Mercy Hospital andMedical Center in Chicago for oncology treatment. As she was receiving her second cycle of intravenous etoposide, she developed an anaphylactic reaction. Five minutes into the etoposide infusion, the patient immediately became dyspneic, tachypneic, tachycardic, and hypotensive, developed generalized pruritus with dermatographia, and had oxygen desaturation. She described feeling a sensation she would refer as “taking me out of the world,” notified the nurse, and the treatment was stopped. Given the instantaneous onset of HSR manifestations, it was concluded that etoposide was responsible because no other chemotherapeutic was being administered. Six days later, she was admitted to the hospital for desensitization to etoposide by the immunology service because etoposide was the most suitable chemotherapeutic option for her condition given the drug’s unique mechanism of action. Castells et al developed a standard 12-step rapid drug desensitization (RDD) protocol that involves the infusion of the target dose in 12 incremental steps over a multiple-hour time span. Following the 12-step RDD protocol, we decided to implement the procedure with slight variations; given the patient’s poor performance status, 2 additional steps were added to administer the dose over a longer time span, giving a total of 14 steps. A premedication treatment was given before desensitization to diminish the risk of breakthrough reactions. This included the following: