The 2022 American Academy of Allergy, Asthma & Immunology (AAAAI) and American College of Allergy, Asthma & Immunology (ACAAI) joint practice parameter update indicates that for patients with a history of immediate hypersensitivity reactions (HSRs) to platinum-based chemotherapeutic agents, the severity of the initial reaction and skin testing results can help guide risk stratification and management, though the overall certainty of evidence is low. Skin testing with platinum agents can help confirm allergy and identify patients who may not require desensitization, but false-negative results have been reported in up to 8-8.5% of cases, and reactions can still occur despite a negative test, particularly if the time since the initial HSR is short (less than six weeks) or long (greater than six months). Risk-stratification protocols using serial skin tests have been shown to safely differentiate allergic from nonallergic patients and reduce unnecessary desensitizations, although they increase operational complexity, cost, and patient burden. Empiric desensitization without prior skin testing remains a safe approach when skin testing is unavailable or impractical, allowing patients to continue first-line therapy. For patients with positive skin tests or confirmed allergy, multi-step desensitization protocols, including the widely reported 12-step method, have been highly successful, with 93-94% of procedures resulting in mild or no reactions and all patients completing therapy. Modified protocols, including a 13-step version and simplified one-bag approaches without drug dilutions, have also demonstrated high efficacy and safety while reducing preparation time and resource requirements, allowing safe continuation of therapy with platinum-based chemotherapeutic agents in patients with prior hypersensitivity. [1]
Published reviews and expert consensus indicate that carboplatin desensitization is recommended for patients who have experienced hypersensitivity reactions and for whom alternative therapies are less effective or unavailable. Skin testing may identify patients at high risk for anaphylaxis during re-exposure. Desensitization protocols induce temporary tolerance by gradually reintroducing small, escalating doses of carboplatin until the full therapeutic dose is administered, and must be repeated for each treatment cycle. Commonly used protocols include multi-step regimens, such as the 12-step rapid desensitization method, as well as shorter 4-8 hour protocols; these involve stepwise increases in drug concentration, controlled infusion rates, and premedication with H1/H2 blockers, corticosteroids, and sometimes leukotriene antagonists. Evidence from a systematic review of 53 studies encompassing 2853 patients, including 44 cases with carboplatin, shows that desensitization success rates for carboplatin range from 67% to 100%, with most breakthrough reactions being mild or moderate and no reported deaths. Desensitization allows patients to safely continue full-dose carboplatin therapy, improving access to first-line treatment while maintaining an acceptable safety profile. [2], [3], [4]
A 2024 retrospective study assessed the effectiveness and safety of a five-step platinum desensitization protocol in patients with high-grade serous adenocarcinoma of the ovary experiencing hypersensitivity to platinum-based chemotherapy. The study analyzed data from 92 patients treated from 2016 to 2020, who had allergies to platinum agents such as cisplatin, carboplatin, oxaliplatin, and nedaplatin. The platinum desensitization protocol outlined involves a strategic five-step approach to acclimate patients to platinum agents, minimizing potential allergic reactions. Initially, the protocol administers dexamethasone, a corticosteroid, at 10 mg orally every 12 hours for two doses to mitigate inflammatory responses. This pre-treatment is followed by diphenhydramine, an antihistamine, given as a 50 mg intramuscular injection to counteract histamine release. The subsequent steps involve administering the platinum agent in progressively increasing concentrations, each diluted in 250 mL of a 5% glucose solution to ensure gradual exposure. The third step introduces a platinum solution at 1/100 of the total dose, infused incrementally: 2 mL/h for 15 minutes, increasing to 20 mL/h. The fourth step involves a higher concentration, 1/10 of the total dose, infused at rates starting from 5 mL/h, doubling to 40 mL/h. The final step administers the remaining dose of platinum, escalating infusion rates from 10 mL/h to 75 mL/h until completion. This meticulous escalation allows for careful monitoring of patient tolerance. [5]
The protocol emphasizes immediate cessation of desensitization upon any signs of allergic reaction, prioritizing patient safety while aiming to maintain the therapeutic use of platinum agents for those with known hypersensitivity. In cases of severe allergic reactions during chemotherapy or desensitization treatment, an immediate emergency response is crucial, involving a multidisciplinary team including oncologists, internists, anesthesiologists, emergency doctors, and nurses. Immediate actions include discontinuing the medication, providing oxygen, keeping the patient warm, and close monitoring of vital signs. Prompt administration of 0.5 to 1 ml of 0.1% epinephrine hydrochloride subcutaneously is recommended, and if symptoms persist, repeated doses or intravenous administration with glucose solutions may be required. Additionally, dexamethasone is administered intravenously, potentially replacing it with hydrocortisone as needed. Antihistamines like promethazine hydrochloride or diphenhydramine are also used. If hypotension persists, supplementary blood volume and vasopressors such as dopamine, alamin, or norepinephrine may be considered. In cases of shock with tracheospasm, intravenous aminophylline and dexamethasone are administered. For cardiac arrest, intracardiac injection of epinephrine and cardiac massage are performed. This comprehensive protocol ensures timely and effective management of severe allergic reactions to potentially life-threatening medications. Overall, this real-world data underscores the feasibility of implementing a structured desensitization protocol for managing platinum hypersensitivity in ovarian cancer treatment, while also emphasizing the importance of patient monitoring and emergency preparedness during therapy. [5]