| Cycle length: 21 days. |
| Drug | Dose and route | Administration | Given on days |
| Rituximab | 375 mg/m2 IV* | Dilute in NS or D5W¶ to a final concentration of 1 to 4 mg/mL. Initial infusion: Start at 50 mg/hour; escalate in 50 mg/hour increments every 30 minutes to a maximum of 400 mg/hour, as tolerated.[2] In the absence of an initial infusion reaction, for subsequent infusions, administer 20% of the total dose over the first 30 minutes and the remaining 80% over 60 minutes, as tolerated. The 90-minute infusion schedule should NOT be used in patients who have clinically significant cardiovascular disease or have a circulating lymphocyte count ≥5000/microL. | Day 0 or 1 |
| 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 |
| Vincristine | 0.4 mg/m2 per day IV (dose not capped) |
| 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 (G-CSF) | | | Start day 6 |
| Pretreatment considerations: |
| Hydration | - Patients receiving cyclophosphamide should maintain adequate oral hydration (2 to 3 L/day) and void frequently to reduce risk of hemorrhagic cystitis.[3]
- Refer to UpToDate topics on hemorrhagic cystitis in cancer patients.
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| Emesis risk | - MODERATE.
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Prophylaxis for infusion reactions | - Premedicate with acetaminophen and diphenhydramine, with or without an H2 receptor blocker, 30 minutes prior to at least the first and second infusions of rituximab.[2]
- Refer to UpToDate topics on infusion reactions to therapeutic monoclonal antibodies used for cancer therapy.
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| Vesicant/irritant properties | - Doxorubicin and vincristine are vesicants; avoid extravasation. Etoposide is an irritant.
- Refer to UpToDate topics 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 G-CSF 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 preexisting liver dysfunction.[3-6] 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; 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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| Hepatitis screening | - Patients should be screened for hepatitis B and C prior to starting rituximab, and, if positive, considered for antiviral prophylaxis.
- Refer to UpToDate topics 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.
|
| 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.
|
| 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 topics on secondary involvement of the CNS by non-Hodgkin 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.[7]
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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 topics 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 dose-adjusted EPOCH-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.
|
- Carriers of hepatitis B or C should be monitored for clinical and laboratory signs of active infection during and following completion of therapy. Rituximab should be discontinued if reactivation occurs.
- Refer to UpToDate topics 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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| 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 ≥500/microL, increase doses by 20% over preceding cycle.
- If ANC <500/microL on one or two measurements, doses remain the same as preceding cycle.
- If ANC <500 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 topics 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. |
