| 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] 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 1 |
| Cyclophosphamide | 750 mg/m2 IV | Dilute in 250 mL NS or D5W¶ and administer over 30 minutes. | Day 1 |
| Doxorubicin | 50 mg/m2 IV | Dilute in 50 mL NS or D5W¶ and administer over three to five minutes. | Day 1 |
| Vincristine | 1.4 mg/m2 IV (max dose 2 mg)Δ | Dilute in 50 mL NS or D5W¶ and administer over 15 to 20 minutes. | Day 1 |
| Prednisone | 100 mg orally | Administer 30 minutes prior to chemotherapy on day 1, then every 24 hours on days 2 to 5. | Days 1 to 5 |
| 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 (30 to 90% risk of emesis).
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
|
| Prophylaxis for infusion reactions | - Premedicate with acetaminophen and diphenhydramine, with or without an H2 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.
|
| Vesicant/irritant properties | - Doxorubicin and vincristine are vesicants; avoid extravasation.
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
|
| Infection prophylaxis | - The risk of febrile neutropenia with this regimen is 10 to 20%;[1] primary prophylaxis with hematopoietic growth factors should be considered on an individual basis, particularly for high-risk patients such as those with preexisting neutropenia, advanced disease, poor performance status, or patients age 65 years or older.
- Refer to UpToDate topics on the use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation.
|
| Dose adjustment for baseline liver or kidney dysfunction | - Adjustment of initial cyclophosphamide, doxorubicin, and vincristine doses may be needed for preexisting liver dysfunction.[3-5] In addition, dose adjustment of cyclophosphamide may be required for kidney dysfunction.
- Refer to UpToDate topics on chemotherapy hepatotoxicity and dose modification in patients with liver disease, conventional cytotoxic agents; chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents; and chemotherapy nephrotoxicity and dose modification in patients with kidney insufficiency, conventional cytotoxic agents.
|
| Hepatitis screening | - Patients should be screened for hepatitis B and C virus prior to starting rituximab, and if positive, considered for antiviral prophylaxis.
- Refer to UpToDate topics on hepatitis B virus reactivation associated with immunosuppressive therapy; 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 | - LVEF should be evaluated 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. Infusion times and schedule may be adjusted to decrease the risk of cardiotoxicity in individuals at high risk for its development.
- Refer to UpToDate topics on clinical manifestations, monitoring, and diagnosis of anthracycline-induced cardiotoxicity and prevention and management of anthracycline cardiotoxicity.
|
| 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 and enterotoxicity of chemotherapeutic agents.
|
| Monitoring parameters: |
- CBC with differential and platelet count weekly during treatment.
|
- Assess basic metabolic panel (creatinine and electrolytes) and liver function prior to each subsequent treatment cycle.
|
- LVEF should be evaluated periodically based on LVEF at initiation of therapy and cumulative dose of doxorubicin.
- 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.
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Treatment should be delayed until ANC is >1500/microL and platelet count is >100,000/microL. If a patient develops grade 4 (ANC <500/microL) neutropenia or febrile neutropenia with any cycle, G-CSF support is added to the regimen for subsequent cycles. If grade 4 neutropenia or febrile neutropenia occurs despite G-CSF support, or if the patient develops grade 3 (25,000 to 50,000/microL) or 4 (<25,000/microL) thrombocytopenia with any cycle, the doses of cyclophosphamide and doxorubicin should be decreased by 50% for subsequent cycles.
|
| Neuropathy | - Dose adjustment of vincristine may be necessary if the severity of neuropathy persists or worsens. No specific guidelines are available for dose adjustments.
|
| If there is a change in body weight of at least 10%, doses should be recalculated. |
