| 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 topic on "Hemorrhagic cystitis in cancer patients".
|
| Emesis risk | - MODERATE (30 to 90% risk of emesis).
- Refer to UpToDate topic on "Prevention and treatment 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 topic on "Infusion reactions to therapeutic monoclonal antibodies used for cancer therapy".
|
| Vesicant/irritant properties | - Doxorubicin and vincristine are vesicants; avoid extravasation.
- Refer to UpToDate topic 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 topic 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 renal 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 renal dysfunction.
- 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" and "Chemotherapy nephrotoxicity and dose modification in patients with renal 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" 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".
|
| 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 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".
|
| 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. |
