Cycle length: 21 days. |
Drug | Dose and route | Administration | Given on days |
Etoposide | 50 mg/m2 per day IV | Dilute a 24-hour supply of etoposide, doxorubicin, and vincristine in 500 mL NS* and administer as continuous infusion over 24 hours per day through central venous line. Solution must be protected from light to maintain stability. | Days 1 to 4 (96 hours) |
Doxorubicin | 10 mg/m2 per day IV | Dilute a 24-hour supply of etoposide, doxorubicin, and vincristine in 500 mL NS* and administer as continuous infusion over 24 hours per day through central venous line. Solution must be protected from light to maintain stability. | Days 1 to 4 (96 hours) |
Vincristine | 0.4 mg/m2 per day IV (dose not capped) | Dilute a 24-hour supply of etoposide, doxorubicin, and vincristine in 500 mL NS* and administer as continuous infusion over 24 hours per day through central venous line. Solution must be protected from light to maintain stability. | Days 1 to 4 (96 hours) |
Cyclophosphamide | 750 mg/m2 IV | Dilute with 250 mL NS or D5W* and administer over 30 minutes. | Day 5 |
Prednisone | 60 mg/m2 orally twice daily | Administer first dose 30 minutes prior to chemotherapy on day 1. | Days 1 to 5 |
Granulocyte colony-stimulating factor | | | Start day 6 |
Pretreatment considerations: |
Emesis risk | - MODERATE.
- Refer to UpToDate topic on "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults".
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Vesicant/irritant properties | - Doxorubicin and vincristine are vesicants; avoid extravasation.
- Etoposide is an irritant.
- Refer to UpToDate topic on "Extravasation injury from chemotherapy and other non-antineoplastic vesicants".
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Infection prophylaxis | - Primary prophylaxis with hematopoietic growth factors is an essential component of this regimen. Regular or pegylated granulocyte colony-stimulating factor may be used according to center policy. In addition, due to the risk of developing Pneumocystis jiroveci pneumonia and other opportunistic infections, consider the use of antimicrobial prophylaxis.[1]
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Dose adjustment for baseline liver or renal dysfunction | - Adjustment of initial cyclophosphamide, doxorubicin, etoposide, and vincristine doses may be needed for pre-existing liver dysfunction.[2-5]
- In addition, dose adjustment of etoposide and cyclophosphamide may be required for renal dysfunction.
- Refer to UpToDate topics on "Chemotherapy nephrotoxicity and dose modification in patients with renal insufficiency: Conventional cytotoxic agents" and "Chemotherapy hepatotoxicity and dose modification in patients with liver disease: Conventional cytotoxic agents" and "Chemotherapy hepatotoxicity and dose modification in patients with liver disease: Molecularly targeted agents".
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Cardiac screening | - Doxorubicin is associated with cardiomyopathy, the incidence of which is related to cumulative dose. Assess baseline LVEF prior to initiation of therapy. Dose alterations should be considered for LVEF <50%, and doxorubicin therapy is contraindicated in patients with LVEF <30% at initiation, those with recent myocardial infarction, severe myocardial dysfunction, severe arrhythmia, or previous therapy with high cumulative doses of doxorubicin or any other anthracyclines.
- Refer to UpToDate topics on "Clinical manifestations, monitoring, and diagnosis of anthracycline-induced cardiotoxicity" and "Prevention and management of anthracycline cardiotoxicity".
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CNS prophylaxis | - The need for CNS prophylaxis is determined based upon the aggressiveness of the tumor reflected in the histology, organ involvement, and presence or absence of high-risk features.
- Refer to UpToDate topic on "Clinical presentation and diagnosis of secondary central nervous system lymphoma".
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HIV screening | - Patients should be screened for HIV prior to starting therapy. Consider reducing the initial dose of cyclophosphamide to 187 mg/m2 if CD4 <100/microL at diagnosis.[6]
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Neurotoxicity | - Vincristine may cause constipation, and in severe cases, paralytic ileus. A routine prophylactic regimen against constipation is recommended in all patients receiving vincristine.
- Refer to UpToDate topic on "Overview of neurologic complications of conventional non-platinum cancer chemotherapy".
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Monitoring parameters: |
- CBC with differential and platelet count twice weekly during treatment.
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- Assess basic metabolic panel (creatinine and electrolytes) and liver function prior to each subsequent treatment cycle.
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- Monitor cumulative doxorubicin dose. Reassess LVEF periodically during daEPOCH-R therapy, as clinically indicated.
- Refer to UpToDate topics on "Clinical manifestations, monitoring, and diagnosis of anthracycline-induced cardiotoxicity" and "Prevention and management of anthracycline cardiotoxicity".
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Suggested dose modifications for toxicity: |
Myelosuppression | - Each new cycle should be delayed until ANC is >1000/microL and platelet count is >100,000/microL. Doses of etoposide, doxorubicin, and cyclophosphamide are adjusted based upon the nadir ANC and platelet counts:[1]
- If nadir ANC is ≥500/microL, increase doses by 20% over preceding cycle.
- If ANC is <500/microL on one or two measurements, doses remain the same as preceding cycle.
- If ANC is <500/microL on ≥3 measurements or platelets <25,000/microL on one measurement, doses reduced by 20% from preceding cycle. Doxorubicin and etoposide doses are not reduced below starting dose.
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Neuropathy | - Dose adjustment of vincristine may be necessary if the severity of neuropathy persists or worsens. No specific guidelines are available for dose adjustments.
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Hepatic dysfunction | - Dose adjustments of vincristine may be necessary in the setting of liver toxicity.
- Refer to UpToDate topic on "Chemotherapy hepatotoxicity and dose modification in patients with liver disease: Conventional cytotoxic agents" and "Chemotherapy hepatotoxicity and dose modification in patients with liver disease: Molecularly targeted agents".
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If there is a change in body weight of at least 10%, doses should be recalculated. |