The dose-adjusted EPOCH-R (DA-EPOCH-R) regimen is a chemotherapy protocol used to treat Burkitt’s lymphoma/DLBCL, which adjusts the doses of certain drugs based on patient tolerance and blood counts.
Dose Adjustment Mechanism
Initial Dosing
– Etoposide (E): 50 mg/m²/day, continuous IV infusion over 24 hours for 4 days (total dose per cycle = 200 mg/m²)
– Doxorubicin (H): 10 mg/m²/day, continuous IV infusion over 24 hours for 4 days (total dose per cycle = 40 mg/m²)
– Vincristine (O): 0.4 mg/m²/day, continuous IV infusion over 24 hours for 4 days (total dose per cycle = 1.6 mg/m²)
– Cyclophosphamide (C): 750 mg/m² IV infusion on day 5
– Prednisolone (P): 60 mg/m² orally twice daily on days 1-5
– Rituximab (R): 375 mg/m² IV infusion on day 1
Adjusting Doses
The doses of etoposide, doxorubicin, and cyclophosphamide are adjusted based on the patient’s blood counts and tolerance to the previous cycle. The primary parameters for dose adjustment are:
- Absolute Neutrophil Count (ANC)
- Platelet Count
- Clinical Toxicity
Criteria for Dose Adjustment
– If ANC nadir is ≥ 500/µL and platelet nadir is ≥ 25,000/µL: Increase the dose by 20% in the next cycle.
– If ANC nadir is < 500/µL or platelet nadir is < 25,000/µL: Maintain the same dose for the next cycle.
– If ANC nadir is < 500/µL for more than 7 days or if febrile neutropenia occurs: Decrease the dose by 20% in the next cycle.
Monitoring and Implementation
– Blood Counts: Blood counts are monitored twice weekly to determine the nadir values.
– Clinical Evaluation: Patients are evaluated for any signs of toxicity, such as febrile neutropenia or other severe side effects.
– Dose Adjustments: Based on the nadir values and clinical evaluation, the doses of etoposide, doxorubicin, and cyclophosphamide are adjusted for the subsequent cycle.
Example of Dose Adjustment
– Cycle 1: Initial doses as per the standard regimen.
– Cycle 2: If the ANC nadir in Cycle 1 was 600/µL and platelet nadir was 30,000/µL, increase the doses of etoposide, doxorubicin, and cyclophosphamide by 20%.
– Cycle 3: If the ANC nadir in Cycle 2 was 400/µL or if the patient experienced febrile neutropenia, decrease the doses by 20%.
CNS Prophylaxis
For high-risk patients, CNS prophylaxis is administered intrathecally:
– Intrathecal Methotrexate: 12 mg on days 1 and 5 of cycles 3 to 6.
Extended CNS Prophylaxis (for CSF involvement)
– Active Treatment: Intrathecal methotrexate 12 mg twice weekly for 4 weeks, then once weekly for 6 weeks, and finally once monthly for 4 months.