Deruxtecan, also known by its brand name Enhertu, is a targeted cancer therapy that combines a monoclonal antibody (trastuzumab) with a chemotherapy agent (deruxtecan, a topoisomerase I inhibitor). This antibody-drug conjugate (ADC) is designed to target specific cancer cells with high precision. Its administration is a strictly controlled process that takes place in a medical setting, such as an oncology clinic or hospital.
The Intravenous Administration Process
The administration of deruxtecan involves several key steps handled by trained healthcare professionals, from preparing the medication to monitoring the infusion. The process ensures the drug is delivered safely and effectively into the patient's bloodstream.
Preparation and Reconstitution
Deruxtecan is supplied as a lyophilized powder in a single-dose vial. The preparation begins with reconstituting the powder with sterile water for injection to create a concentrated solution. This solution is then further diluted with 5% Dextrose Injection, USP, to a final volume suitable for infusion.
Crucial preparation points:
- The reconstituted vial must be swirled gently—never shaken—to prevent foaming.
- Deruxtecan is incompatible with Sodium Chloride Injection (saline) and must be diluted exclusively with 5% Dextrose.
- The final infusion bag must be protected from light throughout the preparation and administration process.
Infusion Delivery
Deruxtecan is administered only as an intravenous infusion, not as an intravenous push or bolus. An infusion pump controls the rate of delivery into a vein. The process requires a dedicated IV line to prevent mixing with other medications. An in-line filter (0.2 or 0.22 micron) is also used during administration.
Treatment Schedule
Treatment with deruxtecan follows a consistent schedule of 3-week (21-day) cycles. The total duration of treatment is determined by the patient's tolerance and whether the cancer continues to respond to the therapy.
Infusion Duration:
- First infusion: This initial infusion is administered over a longer period, typically 90 minutes.
- Subsequent infusions: If the first infusion is well-tolerated, subsequent doses can be administered over a shorter period, usually 30 minutes.
Prophylactic Premedication
Deruxtecan can cause moderate chemotherapy-induced nausea and vomiting. To prevent this, patients are premedicated with a combination of antiemetic medications according to institutional guidelines. A common regimen includes dexamethasone combined with a 5-HT3 receptor antagonist and/or an NK1 receptor antagonist.
Dosage and Management of Side Effects
The dosage of deruxtecan is calculated based on the patient's body weight and the specific type of cancer being treated. The administration also includes protocols for managing adverse reactions and dose adjustments.
Dosage Variation by Cancer Type
- Metastatic Breast Cancer or HER2-Positive Solid Tumors: The standard dose is 5.4 mg/kg IV every 3 weeks.
- Locally Advanced or Metastatic Gastric Cancer: The standard dose is 6.4 mg/kg IV every 3 weeks.
Dose Modification for Adverse Reactions
Adverse reactions may necessitate temporary interruptions, dose reductions, or permanent discontinuation of treatment.
- Infusion-Related Reactions: Symptoms like fever, chills, or breathing difficulties may require slowing or temporarily stopping the infusion. Severe reactions necessitate permanent discontinuation.
- ILD/Pneumonitis: This serious lung condition requires careful monitoring. Asymptomatic (Grade 1) cases warrant interruption until resolved, while Grade 2 or higher cases require permanent discontinuation.
- Neutropenia: Regular complete blood counts are monitored, and treatment may be interrupted or reduced for low neutrophil counts.
- Cardiotoxicity: Baseline and periodic monitoring of left ventricular ejection fraction (LVEF) is recommended to detect any heart function issues.
Missed or Delayed Doses
If a dose is missed or delayed, it should be administered as soon as possible, and the 3-week interval should be maintained for subsequent cycles. The infusion should proceed at the dose and rate tolerated during the most recent session.
Comparison of Deruxtecan Administration Protocols
| Feature | First Infusion | Subsequent Infusions | Management of Reactions |
|---|---|---|---|
| Duration | 90 minutes | 30 minutes (if well-tolerated) | Slow or interrupt infusion rate |
| Frequency | First dose of each treatment cycle | Every 3 weeks thereafter | Adjusts based on the severity of the reaction |
| Monitoring | Close monitoring for infusion-related reactions | Continued monitoring for potential reactions | Permanent discontinuation for severe reactions |
| Preparation | Same reconstitution and dilution protocol | Same reconstitution and dilution protocol | May involve premedication with corticosteroids or antihistamines |
Conclusion
The administration of deruxtecan is a specialized process carried out by trained healthcare professionals in a controlled clinical environment. The specific timing, dosage, and premedication are all tailored to maximize the therapeutic effect while carefully managing potential risks and side effects. Close patient monitoring throughout the infusion and across treatment cycles is a fundamental part of the process, ensuring that any adverse reactions are promptly addressed through dose modification or other supportive care measures. For specific, detailed prescribing information, healthcare professionals refer to sources such as the FDA's drug labeling information for Enhertu.
Important Considerations
It is crucial for patients to understand the importance of following the prescribed schedule, reporting any side effects immediately, and adhering to contraception protocols. The personalized nature of deruxtecan administration, guided by continuous monitoring and proactive management, is a cornerstone of its effectiveness as a targeted cancer therapy. Patients are advised to openly communicate with their healthcare team about any concerns or symptoms experienced during treatment.
