CNS Lymphoma Regimen: Rituximab, Methotrexate, Procarbazine, and Vincristine Followed by Consolidation, Reduced-Dose Whole-Brain Radiotherapy, and Cytarabine (R-MPV → RT + C) Newly Diagnosed Primary CNS Lymphoma
Morris PG et al. J Clin Oncol 2013;31:3971–3979
Shah GD et al. J Clin Oncol 2007;25:4730–4735
Induction Chemotherapy: Five 14-Day Cycles
Premedication for rituximab:
Acetaminophen 650–1000 mg orally, plus
Diphenhydramine 25–50 mg orally or intravenously, 30–60 minutes before starting rituximab
Rituximab 500 mg/m2; administer intravenously in 0.9% sodium chloride injection (0.9% NS) or 5% dextrose injection (D5W), USP, diluted to a concentration within the range 1–4 mg/mL on day 1, every 2 weeks, for 5–7 cycles (total dosage/cycle = 500 mg/m2)
Notes on rituximab administration:
Administer initially at a rate of 50 mg/h. If hypersensitivity or infusion reactions do not occur during the first 30 minutes, increase the rate by 50 mg/h every 30 minutes as tolerated to a maximum rate of 400 mg/h
During subsequent treatments, if previous rituximab administration was well tolerated, start at 100 mg/hour and increase by 100 mg/hour every 30 minutes as tolerated to a maximum rate of 400 mg/hour
Interrupt rituximab administration for fever, chills, edema, congestion of the head and neck mucosa, hypertension, and other serious adverse events. Resume rituximab administration after adverse events abate
Methotrexate 3500 mg/m2; administer intravenously over 2 hours on day 2, every 2 weeks, for 5–7 cycles (total dosage/cycle not including intrathecal therapy = 3500 mg/m2)
Note: For logistical practicality and efficiency, parenteral admixtures containing methotrexate may include a portion or all of the fluid and sodium bicarbonate needed to meet hydration and urinary alkalinization requirements during methotrexate administration
Hydration before, during, and after methotrexate:
Administer 1500–3000 mL/m2 per day. Use a solution containing a total amount of sodium not greater than 0.9% sodium chloride injection (ie, ≤154 mEq/1000 mL), by intravenous infusion during methotrexate administration and for at least 24 hours afterward
Commence fluid administration 2–12 hours before starting methotrexate, depending upon a patient's fluid status
Urine output should be at least 100 mL/h before starting methotrexate infusion
Maintain hydration at a rate that maintains urine output of at least 100 mL/h until the serum methotrexate concentration is <0.05 μmol/L
Adverse effects attributable to methotrexate are related to systemic methotrexate concentrations and the duration for which concentrations are maintained
Sodium bicarbonate 50–150 mEq/1000 mL is added to parenteral hydration solutions to maintain urine pH ≥7.0 to ≤8.0
Leucovorin calcium 25 mg/m2; administer intravenously in 25–250 mL 0.9% NS or D5W over 15–30 minutes every 6 hours starting 24 hours after methotrexate administration began, for at least 72 hours (≥12 doses) or until serum methotrexate concentrations are ≤0.05 μmol/L or undetectable, every 2 weeks, for 5–7 cycles
Vincristine 1.4 mg/m2 (maximum dose = 2.8 mg); administer by intravenous injection over 1–2 minutes on day 2, every 2 weeks, for 5–7 cycles (total dosage/cycle = 1.4 mg/m2; maximum dose/cycle = 2.8 mg)
Procarbazine 100 mg/m2 per day; administer orally for 7 consecutive days on days 1 through 7, only during odd-numbered cycles (cycles 1, 3, 5 ± 7; ie, every 4 weeks) for 3 or 4 cycles (total dosage/cycle = 700 mg/m2)
For patients with cerebrospinal fluid cytologically positive for lymphoma:
Preservative-free methotrexate 12 mg; administer intrathecally via intraventricular catheter or reservoir (eg, Ommaya) once per cycle between days 5 and 8, every 2 weeks, for 5–7 cycles
Supportive Care
Antiemetic prophylaxis
Emetogenic potential on day 1 is MINIMAL
Emetogenic potential on day 2 during odd-numbered cycles (with procarbazine) is MODERATE–HIGH
Emetogenic potential on day 2 during even-numbered cycles (without procarbazine) is MODERATE
See Chapter 39 for antiemetic recommendations
Hematopoietic growth factor (CSF) prophylaxis
Primary prophylaxis is indicated with:
Filgrastim (G-CSF) 5 mcg/kg per day, by subcutaneous injection
Begin use during odd-numbered cycles on day 8 (24 hours after the last dose of procarbazine)
Begin use during even-numbered cycles 24 hours after serum methotrexate concentrations are <0.01 μmol/L(<1 × 10–8 mol/L, <10 nmol/L, or undetectable)
Discontinue daily filgrastim use at least 24 hours before resuming myelosuppressive treatment
See Chapter 43 for more information
Antimicrobial prophylaxis
Risk of fever and neutropenia is INTERMEDIATE
Antimicrobial primary prophylaxis to be considered:
Antibacterial—consider a fluoroquinolone or no prophylaxis; Pneumocystis jirovecii prophylaxis is recommended (eg, cotrimoxazole)
Antifungal—recommended; consider use during periods of neutropenia
Antiviral—antiherpes antivirals (eg, acyclovir, famciclovir, valacyclovir)
See Chapter 47 for more information
Infusion reactions associated with rituximab
Fevers, chills, and rigors
Interrupt rituximab administration for severe symptoms, and give:
Acetaminophen 650 mg; administer orally for fever. For persistent or recurrent symptoms, repeat administration every 4–6 hours as needed during rituximab administration
Diphenhydramine 25–50 mg; administer orally or by intravenous injection for pruritus, hypotension, or angioedema. For persistent or recurrent symptoms, repeat administration every 4–6 hours as needed during rituximab administration
Meperidine 12.5–25 mg; administer by intravenous injection every 10–20 minutes as needed for shaking chills (generally, cumulative doses >100 mg are not needed; use repeated doses with caution in persons with moderate or more severely impaired renal function)
If rituximab administration was interrupted, resume infusion at a slower rate than the maximum rate previously attempted. Rate escalation may be reattempted at smaller incremental steps with close monitoring. Do not exceed the maximum recommended rate of 400 mg/hour
Dyspnea or wheezing without allergic findings (urticaria, or tongue or laryngeal edema)
Interrupt rituximab administration immediately
Give hydrocortisone 100 mg; administer by intravenous injection (or an alternative steroid with equivalent glucocorticoid potency)
Give a histamine (H2) receptor antagonist (ranitidine 50 mg, cimetidine 300 mg, or famotidine 20 mg); administer intravenously over 15–30 minutes
After symptoms resolve, resume rituximab administration at 25 mg/hour with close monitoring. Do not increase the administration rate
CONSOLIDATION AFTER RADIOTHERAPY: TWO 28-DAY CYCLES
Cytarabine 3000 mg/m2 per day (maximum daily dose = 6000 mg); administer intravenously in 25–500 mL 0.9% NS or D5W over 3 hours for 2 days (2 doses), on days 1 and 2, every 28 days (total dosage/cycle = 6000 mg/m2; maximum dose/cycle = 12,000 mg)
Supportive Care
Antiemetic prophylaxis
Emetogenic potential is MODERATE
See Chapter 39 for antiemetic recommendations
Hematopoietic growth factor (CSF) prophylaxis
Primary prophylaxis is indicated with one of the following:
Filgrastim (G-CSF) 5 mcg/kg per day; administer by subcutaneous injection, or
Pegfilgrastim (pegylated filgrastim) 6 mg/0.6 mL; administer by subcutaneous injection for 1 dose
Begin use from 24–72 hours after cytarabine is completed
Continue daily filgrastim use until ANC ≥10,000/mm3 on two measurements separated temporally by ≥12 hours
Discontinue daily filgrastim use at least 24 hours before administering myelosuppressive treatment. Do not administer pegfilgrastim within 14 days before resuming myelosuppressive treatment
See Chapter 43 for more information
Antimicrobial prophylaxis
Risk of fever and neutropenia is INTERMEDIATE
Antimicrobial primary prophylaxis to be considered:
Antibacterial—consider a fluoroquinolone or no prophylaxis; Pneumocystis jirovecii prophylaxis is recommended (eg, cotrimoxazole)
Antifungal—recommended; consider use during periods of neutropenia
Antiviral—antiherpes antivirals (eg, acyclovir, famciclovir, valacyclovir)
See Chapter 47 for more information
Keratitis prophylaxis
Steroid ophthalmic drops (prednisolone 1% or dexamethasone 0.1%) by intraocular instillation daily until 24 hours after high-dose cytarabine is completed
Patients with CSF evidence of malignancy received 12 mg of intra-Ommaya methotrexate between cycles