The R-CODOX-M/IVAC regimen is composed of four cycles, each cycle lasting until the absolute neutrophil count returns to >1000/microL and the platelet count >100,000/microL. Cycles 1 and 3 are R-CODOX-M and cycles 2 and 4 are R-IVAC. Three cycles of R-CODOX-M are sufficient for patients with low-risk disease (ie, a single focus of disease <10 cm in diameter and a normal serum lactate dehydrogenase level). |
R-CODOX-M (cycles 1 and 3):[1-4] |
Rituximab 375 mg/m2 IV on day 1 |
Cyclophosphamide 800 mg/m2 IV on day 1 |
Cyclophosphamide 200 mg/m2 IV on days 2 through 5 |
Doxorubicin 40 mg/m2 slow IV push on day 1 |
Vincristine 1.5 mg/m2 (maximum 2 mg) IV on days 1 and 8 (cycle 1) and days 1 and 8 (cycle 3) |
Methotrexate |
- Age 65 years or younger: 300 mg/m2 IV loading dose over one hour on day 10, followed by 2700 mg/m2 IV infusion administered over the next 23 hours; leucovorin rescue begins 36 hours from the start of the methotrexate infusion
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- Age >65 years: 100 mg/m2 IV loading dose over one hour on day 10, followed by 900 mg/m2 IV infusion administered over the next 23 hours; leucovorin rescue begins 36 hours from the start of the methotrexate infusion
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Granulocyte colony stimulating factor begins 24 hours after leucovorin rescue is started and continues until the absolute neutrophil count is >1000/microL |
Intrathecal medications |
- Intrathecal cytarabine 70 mg (if >3 years of age) on days 1 and 3
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- Intrathecal methotrexate 12 mg (if >3 years of age) on day 15
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- Oral leucovorin 15 mg/dose on day 16, 24 hours after intrathecal methotrexate
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- Enhanced CNS-directed therapy for patients with CNS disease at presentation: cytarabine 70 mg/dose (if >3 years of age) intrathecal (or 15 mg if via Ommaya reservoir) on day 5 and methotrexate 12 mg (if >3 years of age) intrathecal (or 2 mg if via Ommaya reservoir) on day 17 in cycle 1[2]
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R-IVAC (cycles 2 and 4):[1-4] |
Rituximab 375 mg/m2 IV on day 1 |
Ifosfamide |
- Age 65 years or younger: 1500 mg/m2 IV on days 1 through 5 with mesna uroprotection
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- Age >65 years: 1000 mg/m2 IV on days 1 through 5 with mesna uroprotection
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Etoposide 60 mg/m2 IV on days 1 through 5 |
Cytarabine |
- Age 65 years or younger: 2 g/m2 IV every 12 hours on days 1 and 2 (four doses)
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- Age >65 years: 1 g/m2 IV every 12 hours on days 1 and 2 (four doses)
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Granulocyte colony stimulating factor begins 24 hours after the completion of IV chemotherapy and continues until the absolute neutrophil count is >1000/microL |
Intrathecal medications |
- Intrathecal methotrexate 12 mg (if >3 years of age) on day 5
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- Oral leucovorin 15 mg on day 6, 24 hours after intrathecal methotrexate
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- Enhanced CNS-directed therapy for patients with CNS disease at presentation: cytarabine 70 mg (if >3 years of age) intrathecal (or 15 mg if via Ommaya reservoir) on days 7 and 9 in cycle 2[2]
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