Drug Reactions and Desensitization to Chemotherapeutic Agents: An Overview and Case Study (2024)

Earn free contact hours:Click here to connect to the evaluation.Certified nurses can claim no more than 1 total ILNA point for this program. Up to 1 ILNA point may be applied to Oncologic Emergencies OR Oncology Nursing Practice OR Roles of the APRN OR Treatment. Seewww.oncc.orgfor complete details on certification.

The American Cancer Society estimated that there would be more than two million new cancer cases in the United States in 2024, an all-time high (Collins, 2024). Many patients diagnosed with cancer will seek treatment for their disease with systemic therapy. Recent advances in oncology include a plethora of new drugs, some of which use the patient’s immune system to fight the cancer, whereas others have a specific target to stop the cancer cells from growing (e.g., a variant, an antigen, an enzyme, or a pathway that has gone awry within cancer cells) (Brooks, 2023; Olsen et al., 2023). The Cancer Research Catalyst Staff (2024) noted that 2023 brought approvals for 45 oncology drugs, 17 of which were new to the market. Despite newer therapies that have led to more personalized cancer care, standard chemotherapy agents continue to be used as first and subsequent lines of therapy for treating cancer with the intent of stopping or controlling the disease (National Comprehensive Cancer Network [NCCN], 2024b).

Reaction Risk Identification

Common chemotherapy drugs given in acute and ambulatory oncology units that have high reaction rates include the following: platinum-based drugs (carboplatin, oxaliplatin, cisplatin), taxanes (pacl*taxel, docetaxel), etoposide, bleomycin, pegaspargase, and doxorubicin hydrochloride liposome (Olsen et al., 2023). Knowing a drug’s reaction risk and when reactions are commonly encountered with that agent (e.g., with first or second dose versus after multiple exposures and cycles) is a first step in being proactive and ready to manage a reaction.

Oncology nurses can be prepared with several best practice suggestions prior to starting any chemotherapy regimen, including reviewing and reconciling patient allergies; reviewing each medication in the regimen, including the reaction potential of all drugs; administering premedications as ordered and maintaining efficacy time periods (e.g., at least 30–60 minutes); and having a plan in place to intervene immediately with the onset of reaction symptoms. Nurse-driven protocols that include appropriate interventions and specific medications to combat the reaction are helpful and allow for immediate treatment of the patient without having to wait for a physician’s orders (NCCN, 2024b; Olsen et al., 2023). Reactions can start as mild but quickly progress to severe, or even to anaphylaxis, if critical interventions are not implemented at the reaction start (Hall et al., 2023).

Reaction Types and Classifications

Type I–IV Reactions

Many terms are used interchangeably to describe reactions that patients can experience from chemotherapeutic and antineoplastic agents. Some terms include allergic reaction, anaphylaxis, cytokine release syndrome, hypersensitivity reaction, infusion-related reaction, and systemic administration–related reaction. There are distinct differences in each of these reaction types—some are immediate/acute reactions, but others can be delayed (Castells & Solensky, 2023; NCCN, 2024b). According to the Gell and Coombs classification, hypersensitivity reactions are classified into four broad types, as follows: type I (immunoglobulin E (IgE)–mediated hypersensitivity), type II (immunoglobulin G–mediated hypersensitivity), type III (immune complex–mediated hypersensitivity), and type IV (cell-mediated hypersensitivity) reactions (Biga et al., 2019) (see Figure 1). This article will focus on type I, IgE-mediated reactions.

IgE-Mediated Reactions

Castells and Solensky (2023) explained that IgE-mediated reactions occur when a patient is exposed to an antigen or allergen that triggers B cells to produce IgE antibodies. IgE then binds to the surfaces of mast cells or basophils. The next time the patient is exposed to the same antigen, there is a cross-linking of antigens and IgE, which triggers the mast cell to degranulate (break down) and release histamines and cytokines (Vultaggio et al., 2020). This causes the patient to have reaction symptoms that require intervention on most occasions.

Potential Symptoms and Interventions

Acute reaction symptoms can range in severity, with some being mild and involving only one body system (e.g., cutaneous skin reaction with redness or hives), and others being severe and involving multiple body systems (e.g., cutaneous, respiratory, and cardiac), as well as significant changes in vital signs (de Las Vecillas Sánchez et al., 2017; Olsen et al., 2023). Potential acute hypersensitivity reaction symptoms are as follows (Olsen et al., 2023; Shimabukuro-Vornhagen et al., 2018):

• Cardiovascular: chest pain or tightness, hyper- or hypotension, tachycardia
• Cutaneous: itching, redness/flushing, urticaria, rash
• Gastrointestinal: nausea, vomiting, cramping
• Respiratory: shortness of breath, wheezing, stridor, throat tightening, tachypnea, hypoxia
• Other: fever, rigors, lower back pain, sense of impending doom

Interventions for an acute reaction (see Table 1) will depend on the symptom(s), but they can include histamine antagonists to counteract histamine release, steroids to prevent biphasic reaction, albuterol or oxygen for respiratory compromise, epinephrine for anaphylaxis or cardiac arrest, and IV fluids to manage hypotension (Hall et al., 2023).

Common Terminology Criteria for Adverse Events Reaction Types and Grades

Reactions are documented in the patient’s medical record by the specific reaction type and grade. Use of a standard classification and grading system, such as the Common Terminology Criteria for Adverse Events, version 5.0, or the Brown grading system, is suggested (Olsen et al., 2023) (see Tables 2 and 3). Olsen et al. (2023) noted that this allows for objective assessment of reactions and assists in determining appropriate intervention(s). The severity of the reaction will influence the decision regarding complete discontinuation of the drug and recommendation to start an alternate therapy, potential rechallenge of the drug at a slower rate, or consideration to continue the drug via desensitization (NCCN, 2024a, 2024b). Consultation with an allergist may be helpful in developing a drug desensitization (DD) plan for the patient going forward.

DD

DD is a common practice dating back to the first case report in 1942 of a soldier with a penicillin allergy who, at the time, had no alternative antibiotic options (de Las Vecillas Sánchez et al., 2017). According to de Las Vecillas Sánchez et al. (2017), DD has evolved over time, and the first successful IV desensitization with penicillin took place in 1987 and has shaped current DD practices. Common drugs that may require DD include antibiotics, chemotherapy medications, monoclonal antibodies, and biologic agents (de Las Vecillas Sánchez et al., 2017).

DD is a state of temporary tolerance that involves the slow reintroduction of a drug that has previously caused an allergic reaction (Vultaggio et al., 2020). DD takes place in a controlled environment and is not appropriate for every patient who experiences a reaction. Contraindications include extreme allergic responses such as erythema multiforme, skin desquamation, Stevens–Johnson syndrome, and serum sickness (Castells & Solensky, 2023). DD requires multiple doses of premedications to help control and lessen the immune response. Some patients may be instructed to start premedications the night before and morning of the scheduled DD; multiple bags and concentrations of the drug are given at very low doses, with slow administration rates, to ensure patient tolerance (Vultaggio et al., 2020). Altwerger et al. (2017) explained that with each new bag of drug, there are incremental increases in the total dose given (e.g., bag number 1 is 1/1,000 of the total dose, bag number 2 is 1/100 of the total dose). Close observation of the patient is required, and emergency equipment should be readily available in case the patient has a reaction during DD.

Castells and Solensky (2023) noted that breakthrough reaction symptoms during chemotherapy DD occur in about 30% of patients, with only 10% of these reactions being moderate to severe. If the patient tolerates DD, it is required for each subsequent treatment because only temporary drug tolerance is achieved during this procedure (Castells & Solensky, 2023). Patients must have a clear understanding that a DD protocol is necessary each time they receive the offending agent in the future (Hall et al., 2023).

Case Study: Carboplatin Desensitization

E.P. is a 47-year-old female originally diagnosed in 2022 with stage IIIC ovarian cancer based on the International Federation of Gynecology and Obstetrics staging system. The patient underwent exploratory laparotomy with radical hysterectomy, bilateral salpingo-oophorectomy, and tumor debulking. She received six cycles of pacl*taxel, carboplatin, and bevacizumab, then continued maintenance bevacizumab for more than one year. In 2023, she had a rapid rise in serial CA-125 levels, as well as imaging that showed recurrent disease. E.P. was restarted on a regimen of pacl*taxel, carboplatin, and bevacizumab. She tolerated cycle 1 without difficulty but experienced a grade 2 infusion-related reaction to carboplatin with cycle 2 (total cumulative dose of carboplatin at that time, between 2022 and 2023, was eight doses). Her symptoms included cough, shortness of breath, facial flushing, and nausea. The patient was given diphenhydramine, famotidine, and methylprednisolone. Her symptoms were slow to resolve, and she was transferred to the emergency department for further management and observation. After discussion with the patient, her family, and the care team, the decision was made to continue with the current regimen rather than switch to second-line alternate therapy.

Because the patient’s disease was platinum-sensitive and she had previously responded to the chemotherapy in 2022, she would continue with this treatment. To accommodate ambulatory DD within the infusion area’s hours of service, the chemotherapy was split and given on two consecutive days. Pacl*taxel and bevacizumab were given on cycle 3, day 1, and carboplatin DD was given on cycle 3, day 2. E.P. was instructed to take dexamethasone 20 mg by mouth the night before and the morning of the carboplatin DD. When she arrived at the infusion area the morning of the DD, she was given IV premedications of diphenhydramine 50 mg, dexamethasone 20 mg, and famotidine 20 mg. The oncology infusion nurse then waited 30 minutes for the premedications to take effect. The patient was educated about reaction symptoms she should report to the team right away, and the first bag of carboplatin was started (see Table 4 for a breakdown of the number of bags, dilutions, administration time frame, and premedications).

In total, the patient received four bags of carboplatin, each with a different and specific dilution and administration time. Additional premedication of diphenhydramine 25 mg by mouth was given to the patient, per hospital DD protocol, prior to the fourth and final bag of carboplatin. Total chair time was about six hours from start to finish. The patient tolerated the carboplatin DD without difficulty and was able to continue her chemotherapy regimen safely. This case study illustrates how successful DD allowed this patient to remain on a standard-of-care drug for her ovarian cancer.

Implications for Practice

With a clear understanding of desensitization principles, oncology nurses can educate patients by explaining DD procedures, providing education about the risks versus benefits of DD, and reiterating the safety of the procedure. Nurses can help patients make informed treatment decisions that align with their wishes and goals of care. By facilitating shared decision-making discussions between the patient and care team, all treatment options can be reviewed with the patient (e.g., continue with DD or switch to alternative line of therapy), and an appropriate plan of care can be put into place for the patient going forward. DD may be a suitable option if the patient chooses to continue receiving treatment with the chemotherapy agent that caused the reaction.

Conclusion

Oncology nurses have a unique opportunity to support patients through DD. Collaboration between the oncology team and an allergist is encouraged for successful DD. The care team must consider the psychosocial implications of DD, including patient anxiety and fear regarding future reactions, the time commitment necessary for extended drug administration, and the financial implications of missing work frequently for each treatment. Variations in reaction management and DD protocols exist, and a single standard is not appropriate for all scenarios, but oncology nurses can strive to ensure that the practice or procedure that their institution chooses to implement is backed by evidence as well as physician and pharmacy support. DD is a reasonable treatment option that can be offered to patients who would otherwise not be able to continue receiving, at times, a standard-of-care drug to treat their cancer.

About the Author

Maura Price, MSN, RN, AOCNS^®, is an oncology clinical nurse specialist at the Lehigh Valley Topper Cancer Institute in Bethlehem, PA. The author takes full responsibility for this content and did not receive honoraria or disclose any relevant financial relationships. Price can be reached at maura_e.price@lvhn.org, with copy to CJONEditor@ons.org.

References

Altwerger, A., Gressel, G.M., English, D.P., Nelson, W.K., Carusillo, N., Silasi, D.-A., . . . Ratner, E.S. (2017). Platinum desensitization in patients with carboplatin hypersensitivity: A single-institution retrospective study. Gynecologic Oncology, 144(1), 77–82. https://doi.org/10.1016/j.ygyno.2016.09.027

Biga, L.M., Bronson, S., Dawson, S., Harwell, A., Hopkins, R., Kaufmann, J., . . . Runyeon, J. (2019). 21.6 Diseases associated with depressed or overactive immune responses. In Anatomy and physiology. Oregon State University Open Educational Resources Unit & OpenStax. https://bit.ly/45NsnIl

Brooks, K.L. (2023, April 24). Why new cancer treatment discoveries are proliferating. Penn Medicine News. https://bit.ly/4c6hdkk

Brown, S.G.A. (2004). Clinical features and severity grading of anaphylaxis. Journal of Allergy and Clinical Immunology, 114(2), 371–376. https://doi.org/10.1016/j.jaci.2004.04.029

Cancer Research Catalyst Staff. (2024, January 3). FDA approvals in oncology: October–December 2023. American Association for Cancer Research. https://bit.ly/3Xwq3n1

de Las Vecillas Sánchez, L., Alenazy, L.A., Garcia-Neuer, M., & Castells, M.C. (2017). Drug hypersensitivity and desensitizations: Mechanisms and new approaches. International Journal of Molecular Sciences, 18(6), 1316. https://doi.org/10.3390/ijms18061316

Hall, T.R., MacDonald, J.E., Bylinowski, K.M., Alvarez, E.A., Hardesty, M.M., & Smith, J.A. (2023). Management of chemotherapy hypersensitivity reactions and desensitization: An SGO clinical practice statement. Gynecologic Oncology, 177, 180–185. https://doi.org/10.1016/j.ygyno.2023.08.017

National Comprehensive Cancer Network. (2024a). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Breast cancer [v.1.2024]. https://www.nccn.org

National Comprehensive Cancer Network. (2024b). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Ovarian cancer including fallopian tube cancer and primary peritoneal cancer [v.1.2024]. https://www.nccn.org

Olsen, M., LeFebvre, K.B., Walker, S.L., & Prechtel Dunphy, E. (Eds.). (2023). Chemotherapy and immunotherapy: Guidelines and recommendations for practice (2nd ed.). Oncology Nursing Society.

Shimabukuro-Vornhagen, A., Gödel, P., Subklewe, M., Stemmler, H.J., Schlößer, H.A., Schlaak, M., . . . von Bergwelt-Baildon, M.S. (2018). Cytokine release syndrome. Journal for Immunotherapy of Cancer, 6(1), 56. https://doi.org/10.1186/s40425-018-0343-9

Vultaggio, A., Matucci, A., Nencini, F., Bormioli, S., Vivarelli, E., & Maggi, E. (2020). Mechanisms of drug desensitization: Not only mast cells. Frontiers in Pharmacology, 11, 590991. https://doi.org/10.3389/fphar.2020.590991