Chemotherapy Regimens

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Acute Lymphocytic Leukemia

CALGB 8811

(6 modifications)Induction, patients <60 years of age (4-week cycle):Cyclophosphamide: IV: 1200 mg/m2 day 1 [total dose/cycle = 1200 mg/m2]Daunorubicin: IV: 45 mg/m2/dose days 1, 2, and 3 [total dose/cycle = 135 mg/m2]Vincristine: IV: 2 mg/dose days 1, 8, 15, and 22 [total dose/cycle = 8 mg]Prednisone: Oral: 60 mg/m2/dose days 1 to 21 [total dose/cycle = 1260 mg/m2]Asparaginase (E. coli): SubQ: 6000 units/m2/dose days 5, 8, 11, 15, 18, and 22 [total dose/cycle = 36,000 units/m2]Induction, patients ≥60 years of age (4-week cycle):Cyclophosphamide: IV: 800 mg/m2 day 1 [total dose/cycle = 800 mg/m2]Daunorubicin: IV: 30 mg/m2/dose days 1, 2, and 3 [total dose/cycle = 90 mg/m2]Vincristine: IV: 2 mg/dose days 1, 8, 15, and 22 [total dose/cycle = 8 mg]Prednisone: Oral: 60 mg/m2/dose days 1 to 7 [total dose/cycle = 420 mg/m2]Asparaginase (E. coli): SubQ: 6000 units/m2/dose days 5, 8, 11, 15, 18, and 22 [total dose/cycle = 36,000 units/m2]Early intensification (4-week cycle; repeat cycle once):Methotrexate: Intrathecal: 15 mg/dose day 1 [total dose/cycle = 15 mg]Cyclophosphamide: IV: 1000 mg/m2 day 1 [total dose/cycle = 1000 mg/m2]Mercaptopurine: Oral: 60 mg/m2/dose days 1 to 14 [total dose/cycle = 840 mg/m2]Cytarabine: SubQ: 75 mg/m2/dose days 1 to 4 and 8 to 11 [total dose/cycle = 600 mg/m2]Vincristine: IV: 2 mg/dose days 15 and 22 [total dose/cycle = 4 mg]Asparaginase (E. coli): SubQ: 6000 units/m2/dose days 15, 18, 22, and 25 [total dose/cycle = 24,000 units/m2]CNS prophylaxis/interim maintenance (12-week duration; with cranial irradiation days 1 to 12):Methotrexate: Intrathecal: 15 mg/dose days 1, 8, 15, 22, and 29 [total dose/cycle = 75 mg]Mercaptopurine: Oral: 60 mg/m2/dose days 1 to 70 [total dose/cycle = 4200 mg/m2]Methotrexate: Oral: 20 mg/m2/dose days 36, 43, 50, 57, and 64 [total dose/cycle = 100 mg/m2]Late intensification (8-week cycle):Doxorubicin: IV: 30 mg/m2/dose days 1, 8, and 15 [total dose/cycle = 90 mg/m2]Vincristine: IV: 2 mg/dose days 1, 8, and 15 [total dose/cycle = 6 mg]Dexamethasone: Oral: 10 mg/m2/dose days 1 to 14 [total dose/cycle = 140 mg/m2]Cyclophosphamide: IV: 1000 mg/m2 day 29 [total dose/cycle = 1000 mg/m2]Thioguanine: Oral: 60 mg/m2/dose days 29 to 42 [total dose/cycle = 840 mg/m2]Cytarabine: SubQ: 75 mg/m2/dose days 29 to 32 and 36 to 39 [total dose/cycle = 600 mg/m2]Maintenance (continue until 24 months from diagnosis):Vincristine: IV: 2 mg/dose day 1 every 4 weeks [total dose/4 weeks = 2 mg]Prednisone: Oral: 60 mg/m2/dose days 1 to 5 every 4 weeks [total dose/4 weeks = 300 mg/m2]Methotrexate: Oral: 20 mg/m2/dose days 1, 8, 15, and 22 [total dose/phase = 80 mg/m2]Mercaptopurine: Oral: 60 mg/m2/dose days 1 to 28 [total dose/phase = 1680 mg/m2]

CALGB 9111

(6 modifications)Induction, patients <60 years of age (4-week cycle):Cyclophosphamide: IV: 1200 mg/m2 day 1[total dose/cycle = 1200 mg/m2]Daunorubicin: IV: 45 mg/m2/dose days 1, 2, and 3[total dose/cycle = 135 mg/m2]Vincristine: IV: 2 mg/dose days 1, 8, 15, and 22[total dose/cycle = 8 mg]Prednisone: Oral: 60 mg/m2/dose days 1 to 21[total dose/cycle = 1260 mg/m2]Asparaginase (E. coli): SubQ, IM: 6000 units/m2/dose days 5, 8, 11, 15, 18, and 22[total dose/cycle = 36,000 units/m2]Filgrastim: SubQ: 5 mcg/kg/day starting day 4; continue for at least 7 days and until ANC ≥1000/mm3 on two draws, 24 hours apartInduction, patients ≥60 years of age (4-week cycle):Cyclophosphamide: IV: 800 mg/m2 day 1[total dose/cycle = 800 mg/m2]Daunorubicin: IV: 30 mg/m2/dose days 1, 2, and 3[total dose/cycle = 90 mg/m2]Vincristine: IV: 2 mg/dose days 1, 8, 15, and 22[total dose/cycle = 8 mg]Prednisone: Oral: 60 mg/m2/dose days 1 to 7[total dose/cycle = 420 mg/m2]Asparaginase (E. coli): SubQ, IM: 6000 units/m2/dose days 5, 8, 11, 15, 18, and 22[total dose/cycle = 36,000 units/m2]Filgrastim: SubQ: 5 mcg/kg/day starting day 4; continue for at least 7 days and until ANC ≥1000/mm3 on two draws, 24 hours apartEarly intensification (4-week cycle; repeat cycle once):Methotrexate: Intrathecal: 15 mg/dose day 1[total dose/cycle = 15 mg]Cyclophosphamide: IV: 1000 mg/m2 day 1[total dose/cycle = 1000 mg/m2]Mercaptopurine: Oral: 60 mg/m2/dose days 1 to 14[total dose/cycle = 840 mg/m2]Cytarabine: SubQ: 75 mg/m2/dose days 1 to 4 and 8 to 11[total dose/cycle = 600 mg/m2]Vincristine: IV: 2 mg/dose days 15 and 22[total dose/cycle = 4 mg]Asparaginase (E. coli): SubQ, IM: 6000 units/m2/dose days 15, 18, 22, and 25[total dose/cycle = 24,000 units/m2]Filgrastim: SubQ: 5 mcg/kg/day starting day 2; continue at least 14 days and until ANC ≥5000/mm3 on two draws, 24 hours apartCNS prophylaxis/interim maintenance (12-week duration; with cranial irradiation days 1 to 12):Methotrexate: Intrathecal: 15 mg/dose days 1, 8, 15, 22, and 29[total dose/cycle = 75 mg]Mercaptopurine: Oral: 60 mg/m2/dose days 1 to 70[total dose/cycle = 4200 mg/m2]Methotrexate: Oral: 20 mg/m2/dose days 36, 43, 50, 57, and 64[total dose/cycle = 100 mg/m2]Late intensification (8-week cycle):Doxorubicin: IV: 30 mg/m2/dose days 1, 8, and 15[total dose/cycle = 90 mg/m2]Vincristine: IV: 2 mg/dose days 1, 8, and 15[total dose/cycle = 6 mg]Dexamethasone: Oral: 10 mg/m2/dose days 1 to 14[total dose/cycle = 140 mg/m2]Cyclophosphamide: IV: 1000 mg/m2 day 29[total dose/cycle = 1000 mg/m2]Thioguanine: Oral: 60 mg/m2/dose days 29 to 42[total dose/cycle = 840 mg/m2]Cytarabine: SubQ: 75 mg/m2/dose days 29 to 32 and 36 to 39[total dose/cycle = 600 mg/m2]Maintenance (continue until 24 months from diagnosis):Vincristine: IV: 2 mg/dose day 1 every 4 weeks[total dose/4 weeks = 2 mg]Prednisone: Oral: 60 mg/m2/dose days 1 to 5 every 4 weeks[total dose/4 weeks = 300 mg/m2]Mercaptopurine: Oral: 60 mg/m2/dose days 1 to 28[total dose/phase = 1680 mg/m2]Methotrexate: Oral: 20 mg/m2/dose days 1, 8, 15, and 22[total dose/phase = 80 mg/m2]

CLOVE

(relapsed/refractory; persistent minimal residual disease; bridging regimen to hematopoietic stem cell transplant; ≤21 years of age)Clofarabine: IV: 20 to 30 mg/m2/day days 1 to 5[total dose/cycle = 100 to 150 mg/m2]Cyclophosphamide: IV: 300 to 340 mg/m2/day days 1 to 5[total dose/cycle = 1,500 to 1,700 mg/m2]Etoposide: IV: 100 mg/m2/day days 1 to 5[total dose/cycle = 500 mg/m2]

Hyper-CVAD + Imatinib

Cycle A: (Cycles 1, 3, 5, and 7)Imatinib: Oral: 400 mg/day days 1 to 14[total dose/cycle = 5,600 mg]Cyclophosphamide: IV: 300 mg/m2 every 12 hours, for 6 doses, days 1, 2, and 3[total dose/cycle = 1,800 mg/m2]Mesna: IV 600 mg/m2/day continuous infusion days 1, 2, and 3[total dose/cycle = 1,800 mg/m2]Vincristine: IV: 2 mg/day days 4 and 11[total dose/cycle = 4 mg]Doxorubicin: IV: 50 mg/m2/day continuous infusion day 4[total dose/cycle = 50 mg/m2]Dexamethasone: Oral, IV: 40 mg/day days 1 to 4 and 11 to 14[total dose/cycle = 320 mg]Cycle B: (Cycles 2, 4, 6, and 8)Imatinib: Oral: 400 mg/day days 1 to 14[total dose/cycle = 5,600 mg]Methotrexate: IV: 1 g/m2/day continuous infusion day 1[total dose/cycle = 1 g/m2]Leucovorin: IV: 50 mg then 15 mg every 6 hours, for 8 doses (start 12 hours after the end of the methotrexate infusion)[total dose/cycle = 170 mg]Cytarabine: IV: 3 g/m2 every 12 hours for 4 doses, days 2 and 3[total dose/cycle = 12 g/m2]Repeat every 6 weeks in the following sequence: ABABABABCNS ProphylaxisMethotrexate: Intrathecal: 12 mg/day day 2[total dose/cycle = 12 mg/day] or 6 mg into Ommaya day 2[total dose/cycle = 6 mg/day]Cytarabine: Intrathecal: 100 mg/day day 7 or 8[total dose/cycle = 100 mg/day]Repeat cycle every 3 weeks for 3 or 4 cyclesMaintenance (POMP)Imatinib: Oral: 600 mg/day[total dose/cycle = 18,000 mg]Vincristine: IV: 2 mg/dose once each month[total dose/cycle = 2 mg]Prednisone: Oral: 200 mg once daily for 5 days each month (beginning on the day vincristine is administered)[total dose/cycle = 1,000 mg]Repeat cycle every month (except months 6 and 13) for 13 monthsIntensificationImatinib: Oral: 400 mg/day days 1 to 14[total dose/cycle = 5,600 mg]Cyclophosphamide: IV: 300 mg/m2 every 12 hours, for 6 doses, days 1, 2, and 3[total dose/cycle = 1,800 mg/m2]Mesna: IV: 600 mg/m2/day continuous infusion days 1, 2, and 3[total dose/cycle = 1,800 mg/m2]Vincristine: IV: 2 mg/day days 4 and 11[total dose/cycle = 4 mg]Doxorubicin: 50 mg/m2/day continuous infusion day 4[total dose/cycle = 50 mg/m2]Dexamethasone: IV or Oral: 40 mg/day days 1 to 4 and 11 to 14[total dose/cycle = 320 mg]Cycle is given in months 6 and 13 during maintenance

Hyper-CVAD multiple variations

Variation 1:

Cycle A: (Cycles 1, 3, 5, and 7)Cyclophosphamide: IV: 300 mg/m2 every 12 hours, for 6 doses, days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]Mesna: IV: 1,200 mg/m2/day continuous infusion days 1, 2, and 3 [total dose/cycle = 3,600 mg/m2]Vincristine: IV: 2 mg/day days 4 and 11 [total dose/cycle = 4 mg]Doxorubicin: IV: 50 mg/m2 day 4 [total dose/cycle = 50 mg/m2]Dexamethasone: (route not specified): 40 mg/day days 1 to 4 and 11 to 14 [total dose/cycle = 320 mg]Cycle B: (Cycles 2, 4, 6, and 8)Methotrexate: IV: 1 g/m2 continuous infusion day 1 [total dose/cycle = 1g/m2]Leucovorin: (route not specified): 15 mg every 6 hours, for 8 doses (start 12 hours after end of methotrexate infusion) [total dose/cycle = 120 mg]Cytarabine: IV: 3 g/m2 every 12 hours, for 4 doses, days 2 and 3 [total dose/cycle = 12 g/m2]Methylprednisolone: IV: 50 mg twice daily, for 6 doses, days 1, 2, and 3 [total dose/cycle = 300 mg]Repeat every 6 weeks in the following sequence: ABABABAB

CNS ProphylaxisMethotrexate: Intrathecal: 12 mg/day day 2 [total dose/cycle = 12 mg]or 6 mg/day into Ommaya day 2 [total dose/cycle = 6 mg]Cytarabine: Intrathecal: 100 mg day 8 [total dose/cycle = 100 mg]Repeat cycle every 3 weeksMaintenance (POMP)Mercaptopurine: Oral: 50 mg 3 times/day [total dose/cycle = 4,200 to 4,650 mg]Vincristine: IV: 2 mg day 1 [total dose/cycle = 2 mg]Methotrexate: Oral: 20 mg/m2/day days 1, 8, 15, and 22 [total dose/cycle = 80 mg/m2]Prednisone: Oral: 200 mg/day days 1 to 5 [total dose/cycle = 1,000 mg]orMercaptopurine: IV: 1 g/m2/day days 1 to 5 [total dose/cycle = 5 g/m2]Vincristine: IV: 2 mg day 1 [total dose/cycle = 2 mg]Methotrexate: IV: 10 mg/m2/day days 1 to 5 [total dose/cycle = 50 mg/m2]Prednisone: Oral: 200 mg/day days 1 to 5 [total dose/cycle = 1,000 mg]Repeat cycles every month for 2 yearsVariation 2: Cycle A: (Cycles 1, 3, 5, and 7)Cyclophosphamide: IV: 300 mg/m2 every 12 hours, for 6 doses, days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]Mesna: IV: 600 mg/m2/day continuous infusion days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]Vincristine: IV: 2 mg/day days 4 and 11 [total dose/cycle = 4 mg]Doxorubicin: IV: 50 mg/m2 day 4 [total dose/cycle = 50 mg/m2]Dexamethasone: Oral, IV: 40 mg/day days 1 to 4 and 11 to 14 [total dose/cycle = 320 mg]Cycle B: (Cycles 2, 4, 6, and 8)Methotrexate: IV: 1 g/m2 continuous infusion day 1 [total dose/cycle = 1 g/m2]Leucovorin: IV: 50 mg (start 12 hours after end of methotrexate infusion)followed by IV: 15 mg every 6 hours, for 8 doses [total dose/cycle = 170 mg]Cytarabine: IV: 3 g/m2 every 12 hours, for 4 doses, days 2 and 3 [total dose/cycle = 12 g/m2]Repeat every 6 weeks in the following sequence: ABABABABCNS ProphylaxisMethotrexate: Intrathecal: 12 mg day 2 [total dose/cycle = 12 mg]or 6 mg into Ommaya day 2 [total dose/cycle = 6 mg]Cytarabine: Intrathecal: 100 mg day 7 [total dose/cycle = 100 mg]Repeat cycle every 3 weeksVariation 3:Cycle A: (Cycles 1, 3, 5, and 7)Cyclophosphamide: IV: 300 mg/m2 every 12 hours, for 6 doses, days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]Mesna: IV: 600 mg/m2/day continuous infusion days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]Vincristine: IV: 2 mg/day days 4 and 11 [total dose/cycle = 4 mg]Doxorubicin: IV: 50 mg/m2 continuous infusion day 4 [total dose/cycle = 50 mg/m2]Dexamethasone: Oral, IV: 40 mg/day days 1 to 4 and 11 to 14 [total dose/cycle = 320 mg]Cycle B: (Cycles 2, 4, 6, and 8)Methotrexate: IV: 200 mg/m2 day 1 followed by IV: 800 mg/m2 continuous infusion day 1 [total dose/cycle = 1 g/m2]Leucovorin: IV: 50 mg (start 12 hours after end of methotrexate infusion) followed by IV: 15 mg every 6 hours, for 8 doses [total dose/cycle = 170 mg/m2]Cytarabine: IV: 3 g/m2 every 12 hours, for 4 doses, days 2 and 3 [total dose/cycle = 12 g/m2]Repeat every 6 weeks in the following sequence: ABABABABCNS ProphylaxisMethotrexate: Intrathecal: 12 mg day 2 [total dose/cycle = 12 mg]or 6 mg into Ommaya day 2 [total dose/cycle = 6 mg]Cytarabine: Intrathecal: 100 mg day 7 or 8 [total dose/cycle = 100 mg]Repeat cycles every 3 weeks for 6 or 8 cycles Maintenance (POMP)Mercaptopurine: Oral: 50 mg 3 times/day [total dose/cycle = 4,200 to 4,650 mg]Vincristine: IV: 2 mg day 1 [total dose/cycle = 2 mg]Methotrexate: Oral, IV: 20 mg/m2/ day days 1, 8, 15, and 22 [total dose/cycle = 80 mg/m2]Prednisone: Oral: 200 mg/day days 1 to 5 [total dose/cycle = 1,000 mg]or Mercaptopurine: IV: 1 g/m2/day days 1 to 5 [total dose/cycle = 5 g/m2]Vincristine: IV: 2 mg day 1 [total dose/cycle = 2 mg]Methotrexate: IV: 10 mg/m2/day days 1 to 5 [total dose/cycle = 50 mg/m2]Prednisone: Oral: 200 mg/day days 1 to 5 [total dose/cycle = 1,000 mg]Repeat cycles every month (except months 7 and 11 or 9 and 12) for 2 yearsIntensificationEtoposide: IV: 100 mg/m2/day days 1 to 5 [total dose/cycle = 500 mg/m2]Pegaspargase: IV: 2,500 units/m2 day 1 [total dose/cycle = 2,500 units/m2]Given during months 9 and 12 of maintenanceorMethotrexate: IV: 100 mg/m2/day days 1, 8, 15, and 22 [total dose/cycle = 400 mg/m2]Asparaginase: IV: 20,000 units/day days 2, 9, 16, and 23 [total dose/cycle = 80,000 units]Given during months 7 and 11 of maintenanceVariation 4:Cycle A: (Cycles 1, 3, 5, and 7)Cyclophosphamide: IV: 300 mg/m2 every 12 hours, for 6 doses, days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]Mesna: IV: 600 mg/m2/day continuous infusion days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]Vincristine: IV: 2 mg/day days 4 and 11 [total dose/cycle = 4 mg]Doxorubicin: IV: 50 mg/m2day 4 [total dose/cycle = 50 mg/m2]Dexamethasone: (route not specified): 40 mg/day days 1 to 4 and 11 to 14 [total dose/cycle = 320 mg]Cycle B: (Cycles 2, 4, 6, and 8) Methotrexate: IV: 200 mg/m2 day 1followed by IV: 800 mg/m2 continuous infusion day 1 [total dose/cycle = 1 g/m2]Leucovorin: (route not specified): 15 mg every 6 hours, for 8 doses (start 24 hours after end of methotrexate infusion) [total dose/cycle = 120 mg]Cytarabine: IV: 3 g/m2 every 12 hours, for 4 doses, days 2 and 3 [total dose/cycle = 12 g/m2]Methylprednisolone: IV: 50 mg twice daily, for 6 doses, days 1, 2, and 3 [total dose/cycle = 300 mg]Repeat every 6 weeks in the following sequence: ABABABABCNS ProphylaxisMethotrexate: Intrathecal: 12 mg day 2 [total dose/cycle = 12 mg]Cytarabine: Intrathecal: 100 mg day 8 [total dose/cycle = 100 mg]Repeat cycle every 3 weeks for 4 or 8 cyclesMaintenance (POMP)Mercaptopurine: Oral: 50 mg 3 times/day [total dose/cycle = 4,200 to 4,650 mg]Vincristine: IV: 2 mg day 1 [total dose/cycle = 2 mg]Methotrexate: Oral: 20 mg/m2/day days 1, 8, 15, and 22 [total dose/cycle = 80 mg/m2]Prednisone: Oral: 200 mg/day days 1 to 5 [total dose/cycle = 1,000 mg]orMercaptopurine: IV: 1 g/m2/day days 1 to 5 [total dose/cycle = 5 g/m2]Vincristine: IV: 2 mg day 1 [total dose/cycle = 2 mg]Methotrexate: IV: 10 mg/m2/day days 1 to 5 [total dose/cycle = 50 mg/m2]Prednisone: Oral: 200 mg/day days 1 to 5 [total dose/cycle = 1,000 mg]orInterferon alfa: SubQ: 5 million units/m2 daily [total dose/cycle = 140 to 155 million units/m2]Cytarabine: SubQ: 10 mg daily [total dose/cycle = 280 to 310 mg]Repeat cycles every month for 2 yearsVariation 5:

Cycle A: (Cycles 1, 4, 6, and 8)Cyclophosphamide: IV: 300 mg/m2 every 12 hours, for 6 doses, days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]Mesna: IV: 600 mg/m2/day continuous infusion days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]Vincristine: IV: 2 mg/day days 4 and 11 [total dose/cycle = 4 mg]Doxorubicin: IV: 50 mg/m2 continuous infusion day 4 [total dose/cycle = 50 mg/m2]Dexamethasone: Oral, IV: 40 mg/day days 1 to 4 and 11 to 14 [total dose/cycle = 320 mg]Cycle B: (Cycles 3, 5, 7, and 9)Methotrexate: IV: 200 mg/m2 day 1 followed by IV: 800 mg/m2 continuous infusion day 1 [total dose/cycle = 1 g/m2]Leucovorin: IV: 50 mg (start 12 hours after end of methotrexate infusion) followed by IV: 15 mg every 6 hours, for 8 doses [total dose/cycle = 170 mg]Cytarabine: IV: 3 g/m2 every 12 hours, for 4 doses, days 2 and 3 [total dose/cycle = 12 g/m2]Cycle C: Liposomal Daunorubicin/Cytarabine (Cycle 2):Daunorubicin, liposomal: IV: 150 mg/m2/day days 1 and 2 [total dose/cycle = 300 mg/m2]Cytarabine: IV: 1.5 g/m2/day continuous infusion days 1 and 2 [total dose/cycle = 3 g/m2]Prednisone: Oral: 200 mg/day days 1 to 5 [total dose/cycle = 1,000 mg]Administer in the following sequence: ACBABABA (Cycle C does not repeat)CNS ProphylaxisMethotrexate: Intrathecal: 12 mg day 2 [total dose/cycle = 12 mg]or 6 mg into Ommaya day 2 [total dose/cycle = 6 mg]Cytarabine: Intrathecal: 100 mg day 7 or 8 [total dose/cycle = 100 mg]Repeat cycle every 3 weeks for 6 or 8 cyclesMaintenance (POMP)Mercaptopurine: IV: 1 g/m2/day days 1 to 5 [total dose/cycle = 5 g/m2]Vincristine: IV: 2 mg day 1 [total dose/cycle = 2 mg]Methotrexate: IV: 10 mg/m2/day days 1 to 5 [total dose/cycle = 50 mg/m2]Prednisone: Oral: 200 mg/day days 1 to 5 [total dose/cycle = 1,000 mg]Repeat cycles monthly, except months 6, 7, 18, and 19 for 3 yearsIntensificationMethotrexate: IV: 100 mg/m2/day days 1, 8, 15, and 22 [total dose/cycle = 400 mg/m2]Asparaginase: IV: 20,000 units/day days 2, 9, 16, and 23 [total dose/cycle = 80,000 units]Given during months 6 and 18 of maintenanceCyclophosphamide: IV: 300 mg/m2 every 12 hours, for 6 doses, days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]Mesna: IV: 600 mg/m2/day continuous infusion days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]Vincristine: IV: 2 mg/day days 4 and 11 [total dose/cycle = 4 mg]Doxorubicin: IV: 50 mg/m2/day continuous infusion day 4 [total dose/cycle = 50 mg/m2]Dexamethasone: Oral, IV: 40 mg/day days 1 to 4 and 11 to 14 [total dose/cycle = 320 mg]Given during months 7 and 19 of maintenance

LINKER

Remission induction:Daunorubicin: IV: 50 mg/m2/day days 1, 2, and 3 [total dose/cycle = 150 mg/m2]Vincristine: IV: 2 mg/day days 1, 8, 15, and 22 [total dose/cycle = 8 mg]Prednisone: Oral: 60 mg/m2/day days 1 to 28 [total dose/cycle = 1680 mg/m2]Asparaginase: IM: 6000 units/m2/day days 17 to 28 [total dose/cycle = 72,000 units/m2]If residual leukemia in bone marrow on day 14:Daunorubicin: IV: 50 mg/m2 day 15 [total dose/cycle = 50 mg/m2]If residual leukemia in bone marrow on day 28:Daunorubicin: IV: 50 mg/m2/day days 29 and 30 [total dose/cycle = 100 mg/m2]Vincristine: IV: 2 mg/day days 29 and 36 [total dose/cycle = 4 mg]Prednisone: Oral: 60 mg/m2/day days 29 to 42 [total dose/cycle = 840 mg/m2]Asparaginase: IM: 6000 units/m2/day days 29 to 35 [total dose/cycle = 42,000 units/m2]Consolidation therapy:Treatment A (cycles 1, 3, 5, and 7)Daunorubicin: IV: 50 mg/m2/day days 1 and 2 [total dose/cycle = 100 mg/m2]Vincristine: IV: 2 mg/day days 1 and 8 [total dose/cycle = 4 mg]Prednisone: Oral: 60 mg/m2/day days 1 to 14 [total dose/cycle = 840 mg/m2]Asparaginase: IM: 12,000 units/m2/day days 2, 4, 7, 9, 11, and 14 [total dose/cycle = 72,000 units/m2]Treatment B (cycles 2, 4, 6, and 8)Teniposide: IV: 165 mg/m2/day days 1, 4, 8, and 11 [total dose/cycle = 660 mg/m2]Cytarabine: IV: 300 mg/m2/day days 1, 4, 8, and 11 [total dose/cycle = 1200 mg/m2]Treatment C (cycle 9)Methotrexate: IV: 690 mg/m2 continuous infusion over 42 hours day 1 [total dose/cycle = 690 mg/m2]Leucovorin: IV: 15 mg/m2 every 6 hours for 12 doses (start at end of methotrexate infusion) [total dose/cycle = 180 mg/m2]Administer remission induction regimen for one cycle only. Repeat consolidation cycle every 28 days.

MTX/6-MP/VP

(Maintenance)Methotrexate: Oral: 20 mg/m2 weekly [total dose/cycle = 80 mg/m2]Mercaptopurine: Oral: 75 mg/m2/day [total dose/cycle = 2250 mg/m2]Vincristine: IV: 1.5 mg/m2 day 1 [total dose/cycle = 1.5 mg/m2]Prednisone: Oral: 40 mg/m2/day days 1 to 5 [total dose/cycle = 200 mg/m2]Repeat monthly for 2-3 years

POMP

Maintenance:Mercaptopurine: Oral: 50 mg 3 times/day [total dose/cycle = 4200-4650 mg]Methotrexate: Oral: 20 mg/m2 once weekly [total dose/cycle = 80 mg/m2]Vincristine: IV: 2 mg day 1 [total dose/cycle = 2 mg]Prednisone: Oral: 200 mg/day days 1 to 5 [total dose/cycle = 1000 mg]Repeat cycle monthly for 2 years

VAD/CVAD

Induction cycle:Vincristine: IV: 0.4 mg/day continuous infusion days 1 to 4 and 24 to 27 [total dose/cycle = 3.2 mg]Doxorubicin: IV: 12 mg/m2/day continuous infusion days 1 to 4 and 24 to 27 [total dose/cycle = 96 mg/m2]Dexamethasone: Oral: 40 mg/day days 1 to 4, 9 to 12, 17 to 20, 24 to 27, 32 to 35, and 40 to 43 [total dose/cycle = 960 mg]Cyclophosphamide: IV: 1 g/m2 day 24[total dose/cycle = 1 g/m2]Administer one cycle only

Acute Myeloid Leukemia

Clofarabine-Cytarabine

(relapsed/refractory, 18 to 70 years of age)

Induction:Filgrastim: SubQ: 5 mcg/kg (round to nearest vial size) once daily beginning day 0 and continuing until the ANC ≥2,000/mm3 for 2 consecutive daysClofarabine: IV: 25 mg/m2/day over 1 hour days 1 to 5 [total dose/cycle = 125 mg/m2]Cytarabine: IV: 2,000 mg/m2/day over 2 hours days 1 to 5 (beginning 4 hours after start of clofarabine) [total dose/cycle = 10,000 mg/m2]A second induction cycle may be administered after day 21 if needed, up to a maximum of 2 induction cyclesConsolidation:Filgrastim: SubQ: 5 mcg/kg (round to nearest vial size) once daily beginning day 0 and continuing until the ANC ≥2,000/mm3 for 2 consecutive daysClofarabine: IV: 20 mg/m2/day over 1 hour days 1 to 5 [total dose/cycle = 100 mg/m2]Cytarabine: IV: 1,000 mg/m2/day over 2 hours days 1 to 5 (beginning 4 hours after start of clofarabine) [total dose/cycle = 5,000 mg/m2]Repeat consolidation every 21 days for 1 or 2 cycles, up to a maximum of 2 consolidation cycles

Mitoxantrone-Etoposide-Cytarabine

Two variations

Variation 1 (induction):Etoposide: IV: 80 mg/m2/day over 1 hour days 1 to 6 [total dose/cycle = 480 mg/m2]Cytarabine: IV: 1,000 mg/m2/day over 6 hours days 1 to 6 [total dose/cycle = 6,000 mg/m2]Mitoxantrone: IV: 6 mg/m2/day days 1 to 6 (3 hours after the end of the cytarabine infusion) [total dose/cycle = 36 mg/m2]Patients in complete remission proceeded to consolidation therapyVariation 2:Etoposide: IV: 100 mg/m2/day over 2 hours days 1 to 5 [total dose/cycle = 500 mg/m2]Cytarabine: IV: 1,000 mg/m2/day days 1 to 5 [total dose/cycle = 5,000 mg/m2]Mitoxantrone: IV: 8 mg/m2/day days 1 to 5 [total dose/cycle = 40 mg/m2]

CLAG 

Cladribine: IV: 5 mg/m2/day over 2 hours days 1 to 5 [total dose/cycle = 25 mg/m2]

Cytarabine: IV: 2 g/m2/day over 4 hours days 1 to 5 (begin 2 hours after cladribine) [total dose/cycle = 10 g/m2]

Filgrastim: SubQ: 300 mcg daily days 0 to 5 (start 24 hours prior to chemotherapy; for a total of 6 days) [total dose/cycle = 1800 mcg]

May administer a second induction cycle if needed

CLAG-M

Cladribine: IV: 5 mg/m2/day over 2 hour days 1 to 5 [total dose/cycle = 25 mg/m2]Cytarabine: IV: 2 g/m2/day over 4 hours days 1 to 5 (begin 2 hours after cladribine) [total dose/cycle = 10 g/m2]Mitoxantrone: IV: 10 mg/m2/day days 1 to 3 [total dose/cycle = 30 mg/m2]Filgrastim: SubQ: 300 mcg daily days 0 to 5 (start 24 hours prior to chemotherapy; for a total of 6 days) [total dose/cycle = 1800 mcg]May administer a second induction cycle if needed

FLAG

Four variations

Variation 1:Fludarabine: IV: 30 mg/m2/day over 30 minutes days 1 to 5 [total dose/cycle = 150 mg/m2]Cytarabine: IV: 2 g/m2/day over 4 hours days 1 to 5 (begin 4 hours after fludarabine infusion) [total dose/cycle = 10 g/m2]Filgrastim: SubQ: 300 mcg 12 hours prior to start of fludarabine then 300 mcg/day days 2 through 5 [total dose/cycle = 1500 mcg]followed by Filgrastim: SubQ: 300 mcg/day beginning one week after the end of treatment and continuing until complete neutrophil recoveryVariation 2:Fludarabine: IV: 30 mg/m2/day over 30 minutes days 1 to 5 [total dose/cycle = 150 mg/m2]Cytarabine: IV: 2 g/m2/day over 4 hours days 1 to 5 (begin 3.5 hours after end of fludarabine infusion) [total dose/cycle = 10 g/m2]Filgrastim: SubQ: 5 mcg/kg/day beginning 24 hours prior to start of fludarabine and continuing until ANC >500 mm3May repeat cycle one time for partial remissionVariation 3:Fludarabine: IV: 30 mg/m2/day over 30 minutes days 1 to 5 [total dose/cycle = 150 mg/m2]Cytarabine: IV: 2 g/m2/day over 2 hours days 1 to 5 (begin 4 hours after the start of fludarabine infusion) [total dose/cycle = 10 g/m2]Filgrastim: SubQ or IV: 300 mcg/day beginning the day prior to start of chemotherapy and continuing during chemotherapy and until ANC >1000 mm3May receive a second cycleVariation 4:Fludarabine: IV: 25 mg/m2/day over 30 minutes days 1 to 5 [total dose/cycle = 125 mg/m2]Cytarabine: IV: 2 g/m2/day over 4 hours days 1 to 5 (begin 4 hours after start of fludarabine infusion) [total dose/cycle = 10 g/m2]Filgrastim: SubQ: 5 mcg/kg/day beginning 24 hours prior to start of cytarabine and continuing until ANC >500 mm3May repeat cycle in patients with complete remission and partial remission

FLAG-IDA

Three variations

Variation 1:Fludarabine: IV: 30 mg/m2/day over 30 minutes days 1 to 5 [total dose/cycle = 150 mg/m2]Cytarabine: IV: 2 g/m2/day over 4 hours days 1 to 5 (begin 4 hours after the start of fludarabine) [total dose/cycle = 10 g/m2]Idarubicin: IV: 10 mg/m2/day days 1, 2, and 3 [total dose/cycle = 30 mg/m2]Filgrastim: SubQ: 5 mcg/kg from day 6 until ANC >500/mm3Variation 2:Fludarabine: IV: 30 mg/m2/day over 30 minutes days 1 to 5 [total dose/cycle = 150 mg/m2]Cytarabine: IV: 2 g/m2/day over 2 hours days 1 to 5 (begin 4 hours after the start of fludarabine infusion) [total dose/cycle = 10 g/m2]Idarubicin: IV: 8 mg/m2/day over 30 minutes days 1, 2, and 3 [total dose/cycle = 24 mg/m2]Filgrastim: SubQ or IV: 300 mcg/day beginning the day prior to start of chemotherapy and continuing during chemotherapy and until ANC >1000/mm3May receive up to 2 cycles Variation 3:Fludarabine: IV: 30 mg/m2/day over 30 minutes days 1 to 4 [total dose/cycle = 120 mg/m2]Cytarabine: IV: 2 g/m2/day over 4 hours days 1 to 4 (begin 4 hours after fludarabine treatment) [total dose/cycle = 8 g/m2]Idarubicin: IV: 10 mg/m2/day days 1, 2, and 3 [total dose/cycle = 30 mg/m2]Filgrastim: Sub Q: see article for dose and frequency

Cytarabine-Daunorubicin

5 + 2

Induction:Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 5 [total dose/cycle = 500 mg/m2]Daunorubicin: IV: 45 mg/m2/day IV bolus days 1 and 2 [total dose/cycle = 90 mg/m2]May administer a second induction cycle if neededPostremission:Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 5 [total dose/cycle = 500 mg/m2]Daunorubicin: IV: 45 mg/m2/day IV bolus days 1 and 2 [total dose/cycle = 90 mg/m2]Administer 2 courses

Cytarabine-Daunorubicin

7 + 3 (Four variations)

Variation 1:Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 7 [total dose/cycle = 700 mg/m2]Daunorubicin: IV: 45 mg/m2/day IV bolus days 1, 2, and 3 [total dose/cycle = 135 mg/m2]May administer a second induction cycle if neededVariation 2 (≥60 years of age):Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 7 [total dose/cycle = 700 mg/m2]Daunorubicin: IV: 30 mg/m2/day days 1, 2, and 3 [total dose/cycle = 90 mg/m2]May administer a second induction cycle if needed (at a reduced dose of daunorubicin [45 mg/m2])Variation 3 (between 17 and 60 years of age):Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 7 [total dose/cycle = 700 mg/m2]Daunorubicin: IV: 90 mg/m2/day IV bolus days 1, 2, and 3 [total dose/cycle = 270 mg/m2]May administer a second induction cycle if neededVariation 4 (<60 years of age):Cytarabine: IV: 200 mg/m2/day continuous infusion days 1 to 7 [total dose/cycle = 1400 mg/m2]Daunorubicin: IV: 45 mg/m2/day IV bolus days 1, 2, and 3 [total dose/cycle = 135 mg/m2]May administer a second induction cycle if needed

Cytarabine-Daunorubicin-Etoposide

7 + 3 + 7 Induction5 + 2 + 5 Consolidation

Induction:Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 7 [total dose/cycle = 700 mg/m2]Daunorubicin: IV: 50 mg/m2/day days 1, 2, and 3 [total dose/cycle = 150 mg/m2]Etoposide: IV: 75 mg/m2/day over 1 hour days 1 to 7 [total dose/cycle = 525 mg/m2]Up to 3 induction cycles may be given based on individual responseConsolidation:Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 5 [total dose/cycle = 500 mg/m2]Daunorubicin: IV: 50 mg/m2/day IV bolus days 1 and 2 [total dose/cycle = 100 mg/m2]Etoposide: IV: 75 mg/m2/day over 1 hour days 1 to 5 [total dose/cycle = 375 mg/m2]Administer 2 courses

Cytarabine-Idarubicin

7 + 3 Induction – Two variations5 + 2 Consolidation

Induction:Variation 1:Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 7 [total dose/cycle = 700 mg/m2]Idarubicin: IV: 12 mg/m2/day slow IV infusion days 1, 2, and 3 [total dose/cycle = 36 mg/m2]May administer a second induction cycle if neededVariation 2:Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 7 [total dose/cycle = 700 mg/m2]Idarubicin: IV: 13 mg/m2/day slow IV infusion days 1, 2, and 3 [total dose/cycle = 39 mg/m2]May administer a second induction cycle if neededConsolidation:Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 5 [total dose/cycle = 500 mg/m2]Idarubicin: IV: 13 mg/m2/day IV bolus days 1 and 2 [total dose/cycle = 26 mg/m2]Administer 2 courses

Cytarabine-Mitoxantrone

7 + 3 Induction5 + 2 Consolidation

Induction:Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 7 [total dose/cycle = 700 mg/m2]Mitoxantrone: IV: 12 mg/m2/day days 1, 2, and 3 [total dose/cycle = 36 mg/m2]Reinduction if needed:Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 5 [total dose/cycle = 500 mg/m2]Mitoxantrone: IV: 12 mg/m2/day days 1 and 2 [total dose/cycle = 24 mg/m2]Consolidation:Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 5 [total dose/cycle = 500 mg/m2]Mitoxantrone: IV: 12 mg/m2/day days 1 and 2 [total dose/cycle = 24 mg/m2]Administered every 28 days for a total of 2 cycles

Cytarabine-Daunorubicin

Induction:Cytarabine: IV: 2 g/m2/day over 1 hour every 12 hours days 1 to 6 (12 total doses)[total dose/cycle = 24 g/m2]Daunorubicin: IV: 45 mg/m2/day IV bolus days 7 to 9[total dose/cycle = 135 mg/m2]

Cytarabine-Daunorubicin-Etoposide

Daunorubicin: IV: 50 mg/m2/day days 1, 2, and 3[total dose/cycle = 150 mg/m2]Cytarabine: IV: 3 g/m2/dose over 3 hours every 12 hours days 1, 3, 5, and 7 (8 total doses)[total dose/cycle = 24 g/m2]Etoposide: IV: 75 mg/m2/day days 1 to 7[total dose/cycle = 525 mg/m2]Up to 3 induction cycles may be given based on individual response

Cytarabine-Single Agent

Induction – Two variationsConsolidation – Seven variations

Induction:Variation 1 (ages 14 to 50 years):Cytarabine: IV: 3 g/m2 over 2 hours every 12 hours days 1 to 6 (total of 12 doses)[total dose/cycle = 36 g/m2]May administer a second induction cycle if neededVariation 2 (ages >50 years):Cytarabine: IV: 2 g/m2 over 2 hours every 12 hours days 1 to 6 (total of 12 doses)[total dose/cycle = 24 g/m2]May administer a second induction cycle if neededConsolidation:Variation 1: Cytarabine: IV: 3 g/m2 over 3 hours every 12 hours on days 1, 3, and 5 (total of 6 doses)[total dose/cycle = 18 g/m2]Repeat cycle every 4 to 5 weeks (depending on marrow recovery) for a total of 4 postremission cyclesVariation 2: Cytarabine: IV: 400 mg/m2/day continuous infusion on days 1 to 5[total dose/cycle = 2000 mg/m2]Repeat cycle every 4 to 5 weeks (depending on marrow recovery) for a total of 4 postremission cyclesVariation 3: Cytarabine: IV: 100 mg/m2/day continuous infusion on days 1 to 5[total dose/cycle = 500 mg/m2]Repeat cycle every 4 to 5 weeks (depending on marrow recovery) for a total of 4 postremission cyclesVariation 4 (≥60 years of age):Cytarabine: IV: 100 mg/m2/day continuous infusion on days 1 to 5[total dose/cycle = 500 mg/m2]Repeat cycle every 28 days for a total of 4 consolidation cyclesVariation 5 (≤50 years of age):Cytarabine: IV: 3 g/m2 every 12 hours on days 1 to 3 (total of 6 doses)[total dose/cycle = 18 g/m2]Administer a total of 3 consolidation cyclesVariation 6 (>50 years of age)Cytarabine: IV: 2 g/m2 every 12 hours on days 1 to 3 (total of 6 doses)[total dose/cycle = 12 g/m2]Administer a total of 3 consolidation cyclesVariation 7 (>65 years of age):Cytarabine: SubQ: 10 mg/m2/dose every 12 hours days 1 to 14[total dose/cycle = 280 mg/m2]Repeat cycle every 6 weeks for 18 months

Cytarabine-Single Agent-Subcutaneous

Variation 1 (>50 years of age):Cytarabine: SubQ: 20 mg/m2/day days 1 to 14[total dose/cycle = 280 mg/m2]Repeat cycle every 28 days for at least 4 cyclesVariation 2 (>65 years of age):Cytarabine: SubQ: 10 mg/m2/day every 12 hours days 1 to 21[total dose/cycle = 420 mg/m2]After 15 days, a second induction course may be administered if needed

Adenocarcinoma

Capecitabine-Oxaliplatin

Capecitabine: Oral: 1,000 mg/m2 twice daily days 1 to 14, taken with water within 30 minutes after a meal[total dose/cycle = 28,000 mg/m2]Oxaliplatin: IV: 130 mg/m2 day 1[total dose/cycle = 130 mg/m2]Repeat cycle every 21 days for 6 cycles or may continue until clinical benefit no longer realized

Carboplatin-Docetaxel

Docetaxel: IV: 65 mg/m2 over 1 hour day 1 [total dose/cycle = 65 mg/m2]Carboplatin: IV: AUC 6 over 20 minutes day 1[total dose/cycle = AUC = 6]Repeat cycle every 21 days for up to a maximum of 8 cycles

Carboplatin-Etoposide-Paclitaxel

Paclitaxel: IV: 200 mg/m2 over 1 hour day 1[total dose/cycle = 200 mg/m2]Carboplatin: IV: AUC 6 over 20-30 minutes day 1[total dose/cycle = AUC = 6]Etoposide: Oral: 50 mg/day days 1, 3, 5, 7, and 9and Oral: 100 mg/day days 2, 4, 6, 8, and 10 [total dose/cycle = 750 mg]Repeat cycle every 21 days for a total of 4-8 cycles

Carboplatin-Paclitaxel

Carboplatin: IV: Target AUC 6 day 1 [total dose/cycle = AUC = 6]followed byPaclitaxel: IV: 200 mg/m2 infused over 3 hours day 1 [total dose/cycle = 200 mg/m2]Filgrastim: SubQ: 300 mcg/day days 5 to 12 [total dose/cycle = 2400 mcg]Repeat cycle every 21 days for a total of 6 or 8 cycles

Cisplatin-Docetaxel

Two variations

Variation 1:Docetaxel: IV: 75 mg/m2 over 1 hour day 1 [total dose/cycle = 75 mg/m2]Cisplatin: IV: 75 mg/m2 over 1 hour day 1 [total dose/cycle = 75 mg/m2]Repeat cycle every 21 days for up to a total of 8 cyclesVariation 2:Docetaxel: IV: 60 mg/m2 over 1 hour day 1 [total dose/cycle = 60 mg/m2]Cisplatin: IV: 80 mg/m2 over 2 hours day 1 [total dose/cycle = 80 mg/m2]Repeat cycle every 21 days

Cisplatin-Gemcitabine

Gemcitabine: IV: 1250 mg/m2/day days 1 and 8 [total dose/cycle = 2500 mg/m2]Cisplatin: IV: 100 mg/m2 day 1 [total dose/cycle = 100 mg/m2]Repeat cycle every 21 days

Docetaxel-Gemcitabine

Gemcitabine: IV: 1000 mg/m2/day over 30 minutes days 1 and 8 [total dose/cycle = 2000 mg/m2]Docetaxel: IV: 75 mg/m2 over 1 hour day 8 [total dose/cycle = 75 mg/m2]Repeat cycle every 21 days for up to a total of 6 cycles

Acute Promyelocytic Leukemia

Tretinoin-Arsenic Trioxide

Induction (continue until <5% blasts in marrow and no abnormal promyelocytes):Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) day 1 up to day 85 [total induction dose = up to 3825 mg/m2]Arsenic Trioxide: IV: 0.15 mg/kg/day over 1 hour beginning day 10 up to day 85 [total induction dose = up to 11.25 mg/kg]Postremission therapy (beginning with complete remission):Tretinoin: Oral: 45 mg/m2/day weeks 1, 2, 5, 6, 9, 10, 13, 14, 17, 18, 21, 22, 25, 26 [total postremission dose = 4410 mg/m2]Arsenic Trioxide: IV: 0.15 mg/kg/day Monday through Friday weeks 1 to 4, 9 to 12, 17 to 20, and 25 to 28 [total postremission dose = 12 mg/kg]

Tretinoin-Daunorubicin-Cytarabine

Induction, Consolidation and MaintenanceFour variations

Variation 1:Induction:Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) day 1 until complete remission or day 90Daunorubicin: IV: 50 mg/m2/day days 3, 4, 5, and 6 [total dose/cycle = 200 mg/m2]Cytarabine: IV: 200 mg/m2/day continuous infusion for 7 days beginning on day 3 [total dose/cycle = 1,400 mg/m2]Consolidation (begin within 2 to 4 weeks of hematologic remission):Cycles 1 and 2:Arsenic Trioxide: IV: 0.15 mg/kg/day over 1 hour days 1 to 5 for 5 weeks followed by 2 weeks off [total dose/cycle = 3.75 mg/kg]Repeat cycle in 49 days (7 weeks) for a total of 2 cyclesCycles 3 and 4:Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) days 1 to 7 [total dose/cycle = 315 mg/m2]Daunorubicin: IV: 50 mg/m2/day days 1, 2, and 3 [total dose/cycle = 150 mg/m2]Repeat for a total of 2 cyclesMaintenance (if patient remains in complete remission, begin 2 to 4 weeks after recovery from consolidation):Mercaptopurine: Oral: 60 mg/m2 daily for 1 year [total dose/maintenance = 21,900 mg/m2]Methotrexate: Oral: 20 mg/m2 weekly for 1 year [total dose/maintenance = 1,040 mg/m2]Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) days 1 to 7, every other week for 1 year [total dose/maintenance = 8,190 mg/m2]or maintenance with:Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) days 1 to 7, every other week for 1 year [total dose/maintenance = 8,190 mg/m2]Variation 2 (patients ≤60 years of age and WBC <10,000/mm3):Induction:Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) day 1 until hematologic complete remissionDaunorubicin: IV: 60 mg/m2/day days 3, 4, and 5 [total dose/cycle = 180 mg/m2]Cytarabine: IV: 200 mg/m2/day continuous infusion for 7 days beginning on day 3 [total dose/cycle = 1,400 mg/m2]Consolidation:Course 1:Daunorubicin: IV: 60 mg/m2/day days 1, 2, and 3 [total dose/cycle = 180 mg/m2]Cytarabine: IV: 200 mg/m2/day days 1 to 7 [total dose/cycle = 1,400 mg/m2]Course 2:Daunorubicin: IV: 45 mg/m2/day days 1, 2, and 3 [total dose/cycle = 135 mg/m2]Cytarabine: IV: 1,000 mg/m2 every 12 hours for 8 doses days 1 to 4 [total dose/cycle = 8,000 mg/m2]Maintenance:Mercaptopurine: Oral: 50 or 90 mg/m2 daily [total dose/12 week maintenance cycle = 4,200 or 7,560 mg/m2 (84 days)]Methotrexate: Oral: 15 mg/m2 weekly [total dose/12 week maintenance cycle = 180 mg/m2]Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) days 1 to 15 [total dose/12 week maintenance cycle = 675 mg/m2]Repeat cycle every 12 weeks for 2 yearsVariation 3 (patients ≤60 years of age and WBC ≥10,000/mm3):Induction:Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) day 1 until hematologic complete remissionDaunorubicin: IV: 60 mg/m2/day days 3, 4, and 5 [total dose/cycle = 180 mg/m2]Cytarabine: IV: 200 mg/m2/day continuous infusion for 7 days beginning on day 3 [total dose/cycle = 1,400 mg/m2]Consolidation:Course 1:Daunorubicin: IV: 60 mg/m2/day days 1, 2, and 3 [total dose/cycle = 180 mg/m2]Cytarabine: IV: 200 mg/m2/day days 1 to 7 [total dose/cycle = 1,400 mg/m2]Course 2:Daunorubicin: IV: 45 mg/m2/day days 1, 2, and 3 [total dose/cycle = 135 mg/m2]Cytarabine: IV: 2,000 mg/m2 every 12 hours for 10 doses days 1 to 5 (Ades 2006; patients <50 years; Ades 2008) or 1,500 mg/m2 every 12 hours for 10 doses days 1 to 5 (patients 50 to 60 years; Ades 2008) [total dose/cycle = 15,000 mg/m2 to 20,000 mg/m2]Intrathecal prophylaxis: Five intrathecal injections: First dose in between induction and consolidation and 2 doses during each consolidation phase:Methotrexate (preservative free): Intrathecal: 15 mgCytarabine (preservative free): Intrathecal: 50 mgCorticosteroids (preservative free): Intrathecal: Dose unspecifiedMaintenance:Mercaptopurine: Oral: 50 or 90 mg/m2 daily [total dose/12 week maintenance cycle = 4,200 or 7,560 mg/m2 (84 days)]Methotrexate: Oral: 15 mg/m2 weekly [total dose/12 week maintenance cycle = 180 mg/m2]Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) days 1 to 15 [total dose/12 week maintenance cycle = 675 mg/m2]Repeat cycle every 12 weeks for 2 yearsVariation 4 (patients >60 years of age and WBC >10,000/mm3):Induction:Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) day 1 until hematologic complete remissionDaunorubicin: IV: 60 mg/m2/day days 3, 4, and 5 [total dose/cycle = 180 mg/m2]Cytarabine: IV: 200 mg/m2/day continuous infusion for 7 days beginning on day 3[total dose/cycle = 1,400 mg/m2]Consolidation:Course 1:Daunorubicin: IV: 60 mg/m2/day days 1, 2, and 3 [total dose/cycle = 180 mg/m2]Cytarabine: IV: 200 mg/m2/day days 1 to 7 [total dose/cycle = 1,400 mg/m2]Course 2:Daunorubicin: IV: 45 mg/m2/day days 1, 2, and 3 [total dose/cycle = 135 mg/m2]Cytarabine: IV: 1,000 mg/m2 every 12 hours for 8 doses days 1 to 4 [total dose/cycle = 8,000 mg/m2]Intrathecal prophylaxis: Five intrathecal injections: First dose in between induction and consolidation and 2 doses during each consolidation phase:Methotrexate (preservative free): Intrathecal: 15 mgCytarabine (preservative free): Intrathecal: 50 mgCorticosteroids (preservative free): Intrathecal: Dose unspecifiedMaintenance:Mercaptopurine: Oral: 50 or 90 mg/m2 daily [total dose/12 week maintenance cycle = 4,200 or 7,560 mg/m2 (84 days)]Methotrexate: Oral: 15 mg/m2 weekly [total dose/12 week maintenance cycle = 180 mg/m2]Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) days 1 to 15 [total dose/12 week maintenance cycle = 675 mg/m2]Repeat cycle every 12 weeks for 2 years

Tretinoin-Idarubicin

Three variations

Variation 1 (high-risk and ≤60 years of age):Induction:Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) day 1 until complete hematologic remission≤20 years: Oral: 25 mg/m2/day (in 2 divided doses) day 1 until complete hematologic remissionIdarubicin: IV: 12 mg/m2/day days 2, 4, 6, and 8 (omit day 8 for patients >70 years of age) [total dose/cycle = 36 to 48 mg/m2]Consolidation (administer courses sequentially at 1-month intervals for 3 months):Course 1:Idarubicin: IV: 5 mg/m2/day days 1 to 4 [total dose/cycle = 20 mg/m2]Cytarabine: IV: 1,000 mg/m2/day days 1 to 4 [total dose/cycle = 4,000 mg2]Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) days 1 to 15 [total dose/cycle = 675 mg/m2]Course 2:Mitoxantrone: IV: 10 mg/m2/day days 1 to 5 [total dose/cycle = 50 mg/m2]Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) days 1 to 15 [total dose/cycle = 675 mg/m2]Course 3:Idarubicin: IV: 12 mg/m2 day 1 [total dose/cycle = 12 mg/m2]Cytarabine: IV: 150 mg/m2 every 8 hours days 1 to 4 [total dose/cycle = 1,800 mg2]Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) days 1 to 15 [total dose/cycle = 675 mg/m2]Maintenance:Mercaptopurine: Oral: 50 mg/m2 daily [total dose/cycle = 4,500 mg/m2 (90 days)]Methotrexate: IM: 15 mg/m2 weekly [total dose/cycle = 180 mg/m2]Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) days 1 to 15 [total dose/cycle = 675 mg/m2]Repeat cycle every 3 months for 2 yearsVariation 2 (intermediate risk and high risk patients >60 years of age):Induction:TretinoinOral: 45 mg/m2/day (in 2 divided doses) day 1 until complete hematologic remission≤20 years: Oral: 25 mg/m2/day (in 2 divided doses) day 1 until complete hematologic remissionIdarubicin: IV: 12 mg/m2/day days 2, 4, 6, and 8 (omit day 8 for patients >70 years of age) [total dose/cycle = 36 to 48 mg/m2]Consolidation (administer courses sequentially at 1-month intervals for 3 months):Course 1:Idarubicin: IV: 7 mg/m2/day days 1 to 4 [total dose/cycle = 28 mg/m2]Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) days 1 to 15 [total dose/cycle = 675 mg/m2]Course 2:Mitoxantrone: IV: 10 mg/m2/day days 1 to 3 [total dose/cycle = 30 mg/m2]Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) days 1 to 15 [total dose/cycle = 675 mg/m2]Course 3:Idarubicin: IV: 12 mg/m2 days 1 and 2 [total dose/cycle = 24 mg/m2]Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) days 1 to 15 [total dose/cycle = 675 mg/m2]Maintenance:Mercaptopurine: Oral: 50 mg/m2 daily [total dose/cycle = 4,500 mg/m2 (90 days)]Methotrexate: IM: 15 mg/m2 weekly [total dose/cycle = 180 mg/m2]Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) days 1 to 15 [total dose/cycle = 675 mg/m2]Repeat cycle every 3 months for 2 yearsVariation 3 (low risk):Induction:TretinoinOral: 45 mg/m2/day (in 2 divided doses) day 1 until complete hematologic remission≤20 years: Oral: 25 mg/m2/day (in 2 divided doses) day 1 until complete hematologic remissionIdarubicin: IV: 12 mg/m2/day days 2, 4, 6, and 8 (omit day 8 for patients >70 years of age) [total dose/cycle = 36 to 48 mg/m2]Consolidation (administer courses sequentially at 1-month intervals for 3 months):Course 1:Idarubicin: IV: 5 mg/m2/day days 1 to 4 [total dose/cycle = 20 mg/m2]Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) days 1 to 15 [total dose/cycle = 675 mg/m2]Course 2:Mitoxantrone: IV: 10 mg/m2/day days 1 to 3 [total dose/cycle = 30 mg/m2]Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) days 1 to 15 [total dose/cycle = 675 mg/m2]Course 3:Idarubicin: IV: 12 mg/m2 day 1 [total dose/cycle = 12 mg/m2]Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) days 1 to 15 [total dose/cycle = 675 mg/m2]Maintenance:Mercaptopurine: Oral: 50 mg/m2 daily [total dose/cycle = 4,500 mg/m2 (90 days)]Methotrexate: IM: 15 mg/m2 weekly [total dose/cycle = 180 mg/m2]Tretinoin: Oral: 45 mg/m2/day (in 2 divided doses) days 1 to 15 [total dose/cycle = 675 mg/m2]Repeat cycle every 3 months for 2 years

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