Desensitization Protocol for Severe Allergic Reactions to Carboplatin
For patients with a history of severe allergic reactions to carboplatin, the standard 12-step desensitization protocol is the recommended approach, with 94% of procedures resulting in mild or no reactions and all patients able to receive their full target dose. 1, 2
Risk Assessment Before Desensitization
- Patients with BRCA1/BRCA2 mutations have higher risk for carboplatin hypersensitivity reactions (HSRs) and may experience reactions during desensitization 3
- Skin testing between treatments can help identify patients truly allergic to carboplatin, using appropriate non-irritating concentrations (maximum 5 mg/mL for intradermal testing) 1
- Empiric desensitization without skin testing is a safe alternative when testing is not feasible due to limited drug access or institutional policies 1, 3
Standard 12-Step Desensitization Protocol
- The most validated approach uses a 12-step protocol with three sequential solutions of increasing concentration 1, 2
- Protocol begins with extremely diluted concentrations (as low as 1/1,000 of the total dose) and gradually increases to full therapeutic concentration 2, 4
- Each step involves administering progressively larger doses at fixed time intervals (typically 15 minutes per step) 1, 5
- Initial desensitizations should occur in intensive care settings with subsequent infusions potentially in outpatient settings 6, 2
Protocol Variations Based on Reaction History
- For patients who experienced reactions during standard protocol, a modified 13-step protocol with an additional step in the final solution has shown high success rates 1
- Simplified 1-bag protocols have been developed that maintain multiple steps but eliminate the need for drug dilutions, reducing preparation complexity 1
- For very severe previous reactions, more cautious protocols starting with even lower initial doses (0.1 mg) may be necessary 6, 5
Premedication Requirements
- Standard premedication includes antihistamines and corticosteroids (e.g., oral prednisolone 1-2 mg/kg the night before and morning of infusion) 5
- Addition of H2 blockers (e.g., ranitidine) may be beneficial for patients with more severe reaction histories 5
- Premedication alone without desensitization is insufficient to prevent recurrence of hypersensitivity reactions in sensitized patients 6
Safety Considerations
- Emergency medications and equipment must be immediately available during the procedure 6
- Standing orders should be written for immediate intervention if severe reactions occur 6
- Desensitization should be performed by staff trained in managing allergic reactions 3, 6
- Contraindications include previous severe cutaneous adverse reactions (DRESS, SJS, TEN, AGEP) and unstable cardiovascular or respiratory conditions 6
Monitoring During Desensitization
- Most reactions occur during the first desensitization attempt and at the last step of the protocol 2
- Vital signs should be monitored throughout the procedure, with particular vigilance during dose increases 7
- If reactions occur during desensitization, they are typically milder than the initial HSR and can be managed with temporary infusion cessation and additional medications 1, 2
Outcomes and Efficacy
- Studies show 93-94% of desensitization procedures result in mild or no reactions 1
- All patients can typically receive their full target dose despite mild to moderate reactions 2
- Desensitization does not increase overall healthcare costs and maintains equivalent or superior life expectancy compared to alternative treatments 1, 3
Special Considerations
- Basophil activation testing may help identify patients at higher risk for reactions during desensitization, though this remains investigational 1
- Patients with BRCA1/BRCA2 mutations require additional counseling due to higher risk of reactions during desensitization 1, 3
- Desensitization induces temporary tolerance only; the procedure must be repeated for each subsequent drug administration 8, 7