| Cycle length: 28 days. |
| Drug | Dose and route | Administration | Given on days |
| Cycle 1 |
| Rituximab | 375 mg/m2 IV | Dilute in 0.9% NS or D5W* to a final concentration of 1 to 4 mg/mL. Start at 50 mg/hour; escalate in 50 mg/hour increments every 30 minutes to a maximum of 400 mg/hour, as tolerated. | Days 1 and 4 |
| Fludarabine | 25 mg/m2 IV per day | Dilute in 100 mL NS or D5W* and administer over 30 minutes. | Days 1 through 5 |
| Cycles 2 through 6 |
| Rituximab | 375 mg/m2 IV | Dilute in 0.9% NS or D5W* to a final concentration of 1 to 4 mg/mL. Start at 100 mg/hour and escalate in 100 mg/hour increments every 30 minutes to a maximum of 400 mg/hour, as tolerated. | Day 1 |
| Fludarabine | 25 mg/m2 IV per day | Dilute in 100 mL NS or D5W* and administer over 30 minutes. | Days 1 through 5 |
| Pretreatment considerations: |
| Emesis risk | - MINIMAL (<10% frequency of emesis). No scheduled antiemetic prophylaxis is indicated.
- 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.
|
| Prophylaxis for tumor lysis syndrome | - Due to the significant risk of tumor lysis syndrome during the first cycle, all patients should be well hydrated prior to and during therapy and receive allopurinol 300 mg orally once daily beginning the day prior to the first dose of rituximab and continuing for 14 days.[3]
- Refer to UpToDate topics on tumor lysis syndrome.
|
| Infection prophylaxis | - The rate of severe (grade 3/4) infection was 20%.[1] As such, we suggest prophylactic hematopoietic growth factors. In addition, due to the risk of developing Pneumocystis jirovecii pneumonia and other opportunistic infections, consider the use of antimicrobial, antifungal, and antiviral prophylaxis.
- Refer to UpToDate topics on prevention of infections in patients with chronic lymphocytic leukemia and 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 fludarabine may be required for renal dysfunction.[4] Dose adjustment is not needed for rituximab. Dose adjustments for liver impairment are not needed for fludarabine and rituximab.
- Refer to UpToDate topics on 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 infection prior to starting rituximab, and if positive, considered for prophylaxis.
- 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 hepatitis B virus reactivation associated with immunosuppressive therapy.
|
| Monitoring parameters: |
- CBC with differential and platelet count weekly during treatment and as clinically indicated.
|
- Assess renal and hepatic function prior to each cycle and as clinically indicated.
|
- Assess serum creatinine, potassium, phosphate, calcium, uric acid, and LDH daily during treatment for patients at risk for tumor lysis syndrome.
|
- Carriers of hepatitis B or C virus 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: |
| Myelosuppression | - Treatment should be delayed until the ANC is >1000/microL, the platelet count is >80,000/microL, and the hemoglobin is >8 g/dL. Treatment should be delayed until these parameters recover to these values or to within 20% of the baseline counts. For grade 3 hematologic toxicity, subsequent doses of fludarabine should be reduced by 25% from the original dose. If the patient develops grade 4 toxicity, subsequent doses of fludarabine should be reduced by 50% from the original dose.
|
| If there is a change in body weight of at least 10%, doses should be recalculated. |
