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Leukemia

Acute myelogenous leukemia
Induction chemotherapy
Consolidation chemotherapy
Relapsed AML

Acute promyelocytic leukemia
Newly diagnosed
Relapsed APL

Acute lymphocytic leukemia
Linker regimen
CALGB 8811 regimen
Hyper-CVAD/MTX-Ara-C
Refractory and recurrent ALL

Chronic myelogenous leukemia

Chronic lymphocytic leukemia

Hairy cell leukemia 

 

Acute myelogenous leukemia(back to top)

Induction chemotherapy

Cytarabine + Idarubicin (7+3 regimen 1)
Cytarabine (Ara-C) 100 mg/m2/d civi d1-7
Idarubicin 12 mg/m2/d iv d1-3

Wiernik PH et al. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood 1992; 79:313 (link to the article).

Cytarabine + Daunorubicin (7+3 regimen 2)
Cytarabine (Ara-C) 100 mg/m2/d civi d1-7
Daunorubicin 45-60 mg/m2/d iv d1-3

Wiernik PH et al. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood 1992; 79:313 (link to the article).

Preisler H et al. Comparison of three remission induction regimens and two postinduction strategies for the treatment of acute nonlymphocytic leukemia: a Cancer and Leukemia Group B study. Blood 1987; 69: 1441 (link to the article).

Lestaurtinib (CEP701) (for elderly patients)
60-80 mg po bid

Knapper S et al. A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy. Blood 2006; 108:3262 (link to the article). 

Decitabine + Valproic acid (for elderly patients)
Decitabine 15 mg/m2 iv over 1 h qd d1-10
Valproic acid 50 mg/kg po qd d1-10
Q4w

Garcia-Manero G et al. Phase 1/2 study of the combination of 5-aza-2-deoxycytidine with valproic acid in patients with leukemia. Blood 2006; 108:3271 (link to the article).

Consolidation chemotherapy

HDAC
Cytarabine (Ara-C) 3 g/m2 iv q12h x 6 doses d1, 3 and 5 x 4 cycles

Mayer, RJ et al. Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl J Med 1994; 331:896 (link to the article).

Cytarabine + Idarubicin
Cytarabine (Ara-C) 100 mg/m2/d civi d1-5 x 2 cycles
Idarubicin 13 mg/m2/d iv d1-2 x 2 cycles

Wiernik PH et al. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood 1992; 79:313 (link to the article).

Cytarabine + Daunorubicin
Cytarabine (Ara-C) 100 mg/m2/d civi d1-5 x 2 cycles
Daunorubicin 45 mg/m2/d iv d1-2 x 2 cycles

Wiernik PH et al. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood 1992; 79:313 (link to the article).

Cytarabine + Idarubicin ambulatory regimen
Cytarabine (Ara-C) 60 mg/m2 sc infusion q12h  x 10 doses d1-5
Idarubicin 9 mg/m2 iv d1
Qm x 6 cycles

Gardin C et al. Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial. Blood 2007; 109:5129 (link to the article). 

Cytarabine + Daunorubicin ambulatory regimen
Cytarabine (Ara-C) 60 mg/m2 sc infusion q12h  x 10 doses d1-5
Daunorubicin 45 mg/m2 iv d1
Qm x 6 cycles

Gardin C et al. Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy: results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial. Blood 2007; 109:5129 (link to the article).  

Relapsed AML

Mitoxantrone + Etoposide
Mitoxantrone (Novantrone) 10 mg/m2/d iv over 15 min d1-5
Etoposide (VP-16) 100 mg/m2/d iv over 30 min d1-5
If no CR but blast reduction > 50%, a second course is administered
If CR, consolidation chemotherapy with
Mitoxantrone (Novantrone) 8 mg/m2/d iv d1-5
Etoposide (VP-16) 75 mg/m2/d iv d1-5
Cytarabine (Ara-C) 75 mg/m2 iv q12hrs d1-5

Ho, AD et al. Combination of mitoxantrone and etoposide in refractory acute myelogenous leukemia an active and well tolerated regimen. J Clin Oncol 1988; 6:213 (link to the article).

Cytarabine + Mitoxantrone
Cytarabine (Ara-C) 500 mg/m2 iv q12h x 12 doses d1-6
Mitoxantrone (Novantrone) 5 mg/m2/d iv d1-5

Sternberg, DW et al. Treatment of patients with recurrent and primary refractory acute myelogenous leukemia using mitoxantrone and intermediate-dose cytarabine: a pharmacologically based regimen. Cancer 2000; 88:2037 (link to the article).

ADE
Course 1
Cytarabine (Ara-C) 100 mg/m2 iv push q12h d1-10 (20 doses)
Daunorubicin 50 mg/m2 iv slow push d1, 3, 5 (3 doses)
Etoposide (VP-16) 100 mg/m2/d iv over 1 h d1-5 (5 doses)
Course 2
Cytarabine (Ara-C) 100 mg/m2 iv push q12h d1-8 (16 doses)
Daunorubicin 50 mg/m2 iv slow push d1, 3, 5 (3 doses)
Etoposide (VP-16) 100 mg/m2/d iv over 1 h d1-5 (5 doses) 

Milligan DW et al. Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial. Blood 2006; 107:4614 (link to the article). 

FLAG-IDA
Fludarabine 30 mg/m2/d iv over 30 min d1-5
Cytarabine (Ara-C) 2 g/m2/d iv over 4 hrs, 4 hrs after fludarabine, d1-5
Idarubicin 10 mg/m2/d iv d1-3
Filgrastim (Neupogen) 5 mcg/kg/d sc to begin day 6 until neutrophil recovery

Pastore D et al. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Ann Hematol 2003; 82:231 (link to the article). 

Cladribine
Cladribine (2-CdA) 8.9 mg/m2/d civi d1-5

Santana VM et al. 2-Chlorodeoxyadenosine produces a high rate of complete hematologic remission in relapsed acute myeloid leukemia. J Clin Oncol 1992; 10:364 (link to the article).

CLAG
Cladribine (2-CdA) 5 mg/m2/d iv over 2 hrs d1-5
Cytarabine (Ara-C) 2 g/m2/d iv over 4 hrs d1-5
Filgrastim (Neupogen) 300 mcg sc d0-5

Robak T et al. Combination regimen of cladribine (2-chlorodeoxyadenosine), cytarabine and G-CSF (CLAG) as induction therapy for patients with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma 2000; 39:121 (link to the abstract). 

CLAG-M
Cladribine (2-CdA) 5 mg/m2/d iv over 2 hrs d1-5
Cytarabine (Ara-C) 2 g/m2/d iv over 4 hrs starting 2 hrs after cladribine d1-5
Mitoxantrone (Novantrone) 10 mg/m2/d iv d1-3
Filgrastim (Neupogen) 300 mcg sc d0-5
If PR, a second course of CLAG-M is given
Once CR achieved, proceed with following consolidation chemotherapy
Course 1
Cytarabine (Ara-C) 1.5 g/m2/d iv d1-3
Mitoxantrone (Novantrone) 10 mg/m2/d iv d3-5
Course 2
Cytarabine (Ara-C) 2 g/m2 iv q12h x 6 doses d1, 3, 5

Wierzbowska A et al. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol 2008; 80:115 (link to the article).  

Gemtuzumab
Gemtuzumab (Mylotarg) 9 mg/m2 iv q2w x 2 doses

Sievers, EL et al. Efficacy and safety of gemtuzumab ozogamicin in patients with cd33-positive acute myeloid leukemia in first relapse. J Clin Oncol 2001; 19:3244 (link to the article).


Acute promyelocytic leukemia (back to top)

Newly diagnosed

CALGB 9710 regimen


Induction therapy

All trans retinoic acid (ATRA) 45 mg/m2 po qd in 2 divided doses d1 till hematologic CR
Cytarabine (Ara-C) 200 mg/m2/d civi d3-9
Daunorubicin 50 mg/m2/d iv d3-6

Fenaux, P et al. Effect of all trans retinoic acid in newly diagnosed acute promyelocytic leukemia. Results of a multicenter randomized trial. European APL 91 Group. Blood 1993; 82:3241 (link to the article).

Consolidation therapy

Arsenic Trioxide (As2O3) 0.15 mg/kg/d x 5d/week for 5 wks x 2 cycles (cycle 2 starts after 2 wks rest)
followed by
All trans retinoic avid (ATRA) 45 mg/m2 po qd in 2 divided doses d1-7 x 2 cycles
Daunorubicin 50 mg/m2/d iv d1-3 x 2 cycles

Powell BL et al. Effect of consolidation with arsenic trioxide (As2O3) on event-free survival (EFS) and overall survival (OS) among patients with newly diagnosed acute promyelocytic leukemia (APL): North American Intergroup Protocol C9710. 2007 ASCO annual meeting. Abstract 2 (link to the abstract). 

Tallman, MS et al. Acute promyelocytic leukemia: evolving therapeutic strategies. Blood 2002; 99:759 (link to the article).

Maintenance therapy

All trans retinoic avid (ATRA) 45 mg/m2 po qd in 2 divided doses d1-7 qow x 1 year
6-Mercaptopurine (6-MP) 60 mg/m2 po qd x 1 year
Methotrexate (MTX) 20 mg/m2 po qw x 1 year

Tallman, MS et al. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med 1997; 337:1021 (link to the article).

Tallman, MS et al. All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol. Blood 2002; 100:4298 (link to the article).

EAPLG regimen

Age < 60 and WBC < 10,000/uL  

Induction therapy 

All trans retinoic avid (ATRA) 45 mg/m2 po qd in 2 divided doses d1 till hematologic CR
Cytarabine (Ara-C) 200 mg/m2/d civi d3-9
Daunorubicin 60 mg/m2/d iv d3-5

Consolidation therapy

cycle 1
Cytarabine (Ara-C) 200 mg/m2/d civi d1-7
Daunorubicin 60 mg/m2/d iv d1-3

cycle 2
Cytarabine (Ara-C) 1000 mg/m2 iv q12h x 8 doses
Daunorubicin 45 mg/m2/d iv d1-3

Maintenance therapy

All trans retinoic avid (ATRA) 45 mg/m2 po qd in 2 divided doses d1-15 q3m x 2 year
6-Mercaptopurine (6-MP) 90 mg/m2 po qd x 2 year
Methotrexate (MTX) 15 mg/m2 po qw x 2 year

Age < 60 and WBC > 10,000/uL

Induction therapy 

All trans retinoic avid (ATRA) 45 mg/m2 po qd in 2 divided doses d1 till hematologic CR
Cytarabine (Ara-C) 200 mg/m2/d civi d3-9
Daunorubicin 60 mg/m2/d iv d3-5

Consolidation therapy

cycle 1
Cytarabine (Ara-C) 200 mg/m2/d civi d1-7
Daunorubicin 60 mg/m2/d iv d1-3
Intrathecal Cytarabine (Ara-C) 50 mg and Methotrexate (MTX) 15 mg x 3

cycle 2
Cytarabine (Ara-C) 2000 mg/m2 iv q12h x 10 doses
Daunorubicin 45 mg/m2/d iv d1-3
Intrathecal Cytarabine (Ara-C) 50 mg and Methotrexate (MTX) 15 mg x 2

Maintenance therapy

All trans retinoic avid (ATRA) 45 mg/m2 po qd in 2 divided doses d1-15 q3m x 2 year
6-Mercaptopurine (6-MP) 90 mg/m2 po qd x 2 year
Methotrexate (MTX) 15 mg/m2 po qw x 2 year

Age > 60 and WBC < 10,000/uL  

Induction therapy 

All trans retinoic avid (ATRA) 45 mg/m2 po qd in 2 divided doses d1 till hematologic CR
Daunorubicin 60 mg/m2/d iv d3-5

Consolidation therapy

cycle 1 
Daunorubicin 60 mg/m2/d iv d1-3

cycle 2
Daunorubicin 45 mg/m2/d iv d1-3

Maintenance therapy

All trans retinoic avid (ATRA) 45 mg/m2 po qd in 2 divided doses d1-15 q3m x 2 year
6-Mercaptopurine (6-MP) 90 mg/m2 po qd x 2 year
Methotrexate (MTX) 15 mg/m2 po qw x 2 year

Age > 60 and WBC > 10,000/uL  

Induction therapy 

All trans retinoic avid (ATRA) 45 mg/m2 po qd in 2 divided doses d1 till hematologic CR
Cytarabine (Ara-C) 200 mg/m2/d civi d3-9
Daunorubicin 60 mg/m2/d iv d3-5

Consolidation therapy

cycle 1
Cytarabine (Ara-C) 200 mg/m2/d civi d1-7
Daunorubicin 60 mg/m2/d iv d1-3
Intrathecal Cytarabine (Ara-C) 50 mg and Methotrexate (MTX) 15 mg x 3

cycle 2
Cytarabine (Ara-C) 1000 mg/m2 iv q12h x 8 doses
Daunorubicin 45 mg/m2/d iv d1-3
Intrathecal Cytarabine (Ara-C) 50 mg and Methotrexate (MTX) 15 mg x2

Maintenance therapy

All trans retinoic avid (ATRA) 45 mg/m2 po qd in 2 divided doses d1-15 q3m x 2 year
6-Mercaptopurine (6-MP) 90 mg/m2 po qd x 2 year
Methotrexate (MTX) 15 mg/m2 po qw x 2 year 

Ades L et al. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol 2006; 24:5703 (link to the article).

ATRA + Arsenic Trioxide
All trans retinoic avid (ATRA) 45 mg/m2 po qd in 2 divided doses d1 till CR
Arsenic Trioxide (As2O3) 0.15 mg/kg/d iv over 1 h d10 till CR
If WBC > 10 x 109/L, add
Gemtuzumab (Mylotarg) 9 mg/m2 iv d1 and/or
Idarubicin 12 mg/m2/d iv d1-4
Once CR obtained, change to
All trans retinoic avid (ATRA) 45 mg/m2 po qd in 2 divided doses 2 wks on and 2 wks off x 28 wks
Arsenic Trioxide (As2O3) 0.15 mg/kg/d iv d1-5 qw 4 wks on and 4 wks off x 28 wks

Tsimberidou AM et al. Clinical outcomes and rates of molecular remission with all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) combination therapy in newly diagnosed acute promyelocytic leukemia (APL). 2006 ASCO annual meeting. Abstract 6503. (link to the article)

Estey E et al. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood 2006; 107:3469 (link to the article). 

Relapsed APL

Arsenic Trioxide
Arsenic Trioxide (As2O3) Induction arsenic trioxide 0.15 mg/kg iv qd till marrow remission (median 35 doses)
3-4 wks after induction, consolidation arsenic trioxide 0.15 mg/kg iv qd x 25 days over 5 wks

Soignet, SL et al. United states multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol 2001; 19:3852 (link to the article).

Shen, ZX et al. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood 1997; 89:3354 (link to the article).

Niu, C et al. Studies on treatment of acute promyelocytic leukemia with arsenic trioxide: remission induction, follow-up, and molecular monitoring in 11 newly diagnosed and 47 relapsed acute promyelocytic leukemia patients. Blood 1999; 94:3315 (link to the article).


Acute lymphoblastic leukemia (back to top)

Linker regimen

Induction chemotherapy

Daunorubicin 50 mg/m2/d iv d1-3
Vincristine 2 mg iv d 1, 8, 15 and 22
Prednisone 60 mg/m2/d po d1-28
L-Asparaginase 6000 U/m2/d im d17-28
If bone marrow on d14 has residual leukemia
Daunorubicin 50 mg/m2 iv d15
If bone marrow on d28 has residual leukemia
Daunorubicin 50 mg/m2 iv d29 and 30
Vincristine 2 mg iv d29 and 36
Prednisone 60 mg/m2/d po d29-42
L-Asparaginase 6000 U/m2/d im d29-35

Consolidation chemotherapy

Treatment A (cycle 1, 3, 5, 7)
Daunorubicin 50 mg/m2/d iv d1-2
Vincristine 2 mg iv d 1, 8
Prednisone 60 mg/m2/d po d1-14
L-Asparaginase 12000 U/m2 im d2, 4, 7, 9, 11, 14
Treatment B (cycle 2,4,6,8)
Teniposide 165 mg/m2 iv d1, 4, 8, 11
Cytarabine (Ara-C) 300 mg/m2 iv d1, 4, 8, 11
Treatment C (cycle 9)
Methotraxate (MTX) 690 mg/m2 iv over 42 hrs
Leucovorin 15 mg/m2 iv q6h x 12 doses beginning at 42 hrs

Maintenance chemotherapy

Methotrexate (MTX) 20 mg/m2 po qw x 30 months
6-Mercaptopurine (6-MP) 75 mg/m2 po qd x 30 months

CNS prophylaxis

Begin within 1 wk of CR
Cranial radiation 1.8 Gy/d to 18 Gy
Intrathecal Methotrexate (MTX) 12 mg qw x 6 wks

CNS treatment

In patients with CNS involvement, start intrathecal chemotherapy during induction chemotherapy.
Intrathecal Methotrexate (MTX) 12 mg qw x 10 wks, then qm x 9 months
Cranial radiation 1.8 Gy/d to 28 Gy

Linker CA et al. Improved results of treatment of adult acute lymphoblastic leukemia. Blood 1987; 69:1242 (link to the article).

Linker CA et al. Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report. Blood 1991; 78:2814 (link to the article).

CALGB 8811 regimen

Course I: Induction (4 wks)

Cyclophosphamide (Cytoxan) 1200 mg/m2 (800 mg/m2 if pts older than 60) iv d1
Daunorubicin 45 mg/m2/d (30 mg/m2/d if pts older than 60) iv d1-3
Vincristine 2 mg iv d1, 8, 15, 22
Prednisone 60 mg/m2/d po d1-21 (d1-7 if pts older than 60)
L-Asparaginase 6000 U/m2 sc d5, 8, 11, 15, 18, 22

Course II: Early intensification (4 wks/cycle x 2 cycles)

Intrathecal methotraxate (MTX) 15 mg d1
Cyclophosphamide (Cytoxan) 1000 mg/m2 iv d1
6-Mercaptopurine (6-MP) 60 mg/m2/d po d1-14
Cytarabine (Ara-C) 75 mg/m2/d sc d1-4, 8-11
Vincristine 2 mg iv d15, 22
L-Asparaginase 6000 IU/m2 sc d15, 18, 22, 25

Course III: CNS prophylaxis and interim maintenance (12 wks)

Cranial radiation 2,400 cGy d1-12
Intrathecal methotraxate (MTX) 15 mg d1, 8, 15, 22, 29
6-Mercaptopurine (6-MP) 60 mg/m2/d po d1-70
Methotraxate (MTX) 20 mg/m2 po d36, 43, 50, 57, 64

Course IV: Late intensification (8 wks)

Daunorubicin 30 mg/m2 iv d1, 8, 15
Vincristine 2 mg iv d1, 8, 15
Dexamethasone (Decadron) 10 mg/m2/d po d1-14
Cyclophosphamide (Cytoxan) 1000 mg/m2 iv d29
6-Thioguanine 60 mg/m2/d po d29-42
Cytarabine (Ara-C) 75 mg/m2/d sc d29-32, 36-39

Course V: Prolonged maintenance (until 24 months from diagnosis)

Vincristine 2 mg iv d1
Prednisone 60 mg/m2/d po d1-5
Methotraxate (MTX) 20 mg/m2 po d1, 8, 15, 22
6-Mercaptopurine (6-MP) 80 mg/m2/d po d1-28
Q4w

Larson R et al. A five-drug regimen remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: Cancer and Leukemia Group B Study 8811. Blood 1995; 85:2025 (link to the article).

Hyper-CVAD/MTX-Ara-C

Cycle 1,3,5,7 (3-4 wks/cycle)

Cyclophosphamide (Cytoxan) 300 mg/m2 iv over 2 hrs q12 hrs x 6 doses d1-3
Mesna 600 mg/m2/d civi d1-3 to start 1 h before cyclophosphamide till 12 hrs after completion of cyclophosphamide
Vincristine 2 mg iv d4, 11
Doxorubicin (Adriamycin) 50 mg/m2 iv over 24 hrs d4
Dexamethasone (Decadron) 40 mg po qd d1-4 and d11-14

Cycle 2,4,6,8 (3-4 wks/cycle)

Methotrexate (MTX) 200 mg/m2 iv over 2 hrs followed by 800 mg/m2 civi over 22 hrs d1
Cytarabine (Ara-C) 3 g/m2 (1 g/m2 for patients over 60 years old) iv over 2 hrs q12 hrs x 4 doses d2-3
Leucovorin 50 mg iv q6 hrs starting 12 hrs after completion of MTX till MTX level < 0.05 uM

Intrathecal chemotherapy

Prophylaxis
Methotrexate (MTX) 12 mg d2 of each cycle for a total of 3-4 treatments
Cytarabine (Ara-C) 100 mg d8 of each cycle for a total of 3-4 treatments

Therapeutic
Intrathecal chemotherapy twice a week (Methotrexate (MTX) 12 mg and Cytarabine (Ara-C) 100 mg respectively) till no more cancer cells in CSF, then decrease intrathecal chemotherapy to once a week x 4, followed by Methotrexate (MTX) 12 mg d2, Cytarabine (Ara-C) 100 mg d8 for the remaining chemotherapy cycles

Support care

Cipro 500 mg po bid
Fluconazole 200 mg po qd
Acyclovir 200 mg po bid
Filgrastim (Neupogen) 10 mcg/kg sc qd to start on d5 of hyperCVAD and d4 of high dose methotraxate and cytarabine

Kantarjian H et al. Results of treatment with hyper-CVAD, a dose-intensive regimen in adult acute lymphoblastic leukemia. J Clin Oncol 2000; 18:547 (link to the article).

Thomas DA et al. Outcome with the hyper-CVAD regimens in lymphoblastic leukemia. Blood 2004; 104:1624 (link to the article).

Refractory and recurrent ALL

Cytarabine + Idarubicin
Cytarabine (Ara-C) 3 g/m2/d iv over 3 hrs d1-5
Idarubicin 40 mg/m2 iv d3

Weiss, MA et al. A single, high dose of idarubicin combined with cytarabine as induction therapy for adult patients with recurrent or refractory acute lymphoblastic leukemia. Cancer 2002; 95:581 (link to the article).

Cytarabine + Idarubicin (7+3 regimen)
Cytarabine (Ara-C) 100 mg/m2/d civi d1-7
Idarubicin 12 mg/m2/d iv d1-3

Karbasian-Esfahani, M et al. Idarubicin and standard-dose cytosine arabinoside in adults with recurrent and refractory acute lymphocytic leukemia. Cancer 2004; 101:1414 (link to the article).

Imatinib (for Ph-positive ALL)
Imatinib (Gleevec) 600 mg po qd

Approved by FDA on 10/19/06 (link to FDA site).

Ottmann OG et al. A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias. Blood 2002; 100: 1965 (link to the article).

Dasatinib (for Ph-positive ALL)
Dasatinib (Sprycel) 70 mg po bid

Approved by FDA on 6/28/06 (link to FDA file). 

Ottman O et al. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study. Blood 2007; 110: 2309 (link to the article).

Talpaz M et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Eng J Med 2006; 354:2531 (link to the article).

Nilotinib
Nilotinib (Tasigna) (for Ph-positive ALL)
400-600 mg po bid

Kantarjian H et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Eng J Med 2006; 354:2542 (link to the article).

Nelarabine (for T-cell ALL)
Nelarabine 1.5 g/m2/d (5 mg/ml) iv over 2 hrs d1, 3, 5
For 3 cycles

DeAngelo DJ et al. Nelarabine induces complete remission in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801. Blood 2007; 109:5136 (link to the article). 


Chronic myelogenous leukemia (back to top)

Imatinib 
Imatinib (Gleevec) 400-800 mg po qd

de Lavallade H et al. Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol 2008; 26:3358 (link to the article).

Pye SM et al. The effects of imatinib on pregnancy outcome. Blood 2008; 111:5505 (link to the article).  

Hochhaus A et al. Favorable long-term follow-up results over 6 years for response, survival, and safety with imatinib mesylate therapy in chronic-phase chronic myeloid leukemia after failure of interferon-a treatment. Blood 2008; 111:1039 (link to the article). 

Palandri F et al. Long-term outcome of complete cytogenetic responders after imatinib 400 mg in late chronic phase, Philadelphia-positive chronic myeloid leukemia: the GIMEMA Working Party on CML. J Clin Oncol 2008; 26:106 (link to the article). 

Druker BJ et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006; 355:2408 (link to the article). 

Kantarjian HM et al. Survival benefit with imatinib mesylate  versus interferon-a-based regimens in newly diagnosed chronic-phase chronic myelogenous leukemia. Blood 2006; 108:1835 (link to the article). 

O’Brien SG et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003; 348:994 (link to the article).

Kantarjian H et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 2002; 346:645 (link to the article).  

Druker BJ et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myelogenous leukemia. N Engl J Med 2001; 344:1031 (link to the article)

Druker BJ et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of  chronic myeloid leukemia or acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 2001; 344:1038 (link to the article).

Dasatinib
Dasatinib (Sprycel) 70 mg po  bid or 100 mg po qd

Approved by FDA on 6/28/2006 (link to FDA file).

Tam CS et al. Failure to achieve a major cytogenetic response by 12 months defines inadequate response in patients receiving nilotinib or dasatinib as second or subsequent line therapy for chronic myeloid leukemia. Blood 2008; 112:516 (link to the article).

Atallah EL et al. Use of dasatinib in patients (pts) with previously untreated chronic myelogenous leukemia (CML) in chronic phase (CML-CP). 2007 ASCO annual meeting. Abstract 7005 (link to the abstract).  

Kantarjian H et al. Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial. Blood 2007; 109:5143 (link to the article). 

Guilhot F et al. Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase. Blood 2007; 109:4143 (link to the article). 

Cortes J et al. Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Blood 2007; 109:3207 (link to the article).

Hochhaus A et al. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood 2007; 109:2303 (link to the article). 

Quintas-Cardama A et al. Dasatinib (BMS-354825) is active in Philadelphia chromosome-positive chronic myelogenous leukemia after imatinib and nilotinib (AMN107) therapy failure. Blood 2007; 109:497 (link to the article).

Hochhaus A et al. Dasatinib (SPRYCEL) 50 mg or 70 mg bid versus 100 mg or 140 mg qd in patients with chronic myeloid leukemia in chronic phase (CML-CP) resistant or intolerant to imatinib: results of the CA 180-034 study. 2006 ASH annual meeting. Abstract 166 (link to the abstract).

Talpaz M et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Eng J Med 2006; 354:2531 (link to the article).

Nilotinib
Nilotinib (Tasigna) 400-600 mg po bid
Avoid food 2 hours before and 1 hour after taking a dose
Prolongs QT interval. Should not be used in patients with hypokalemia, hypomagnesemia or long QT syndrome. Obtain ECGs to monitor QTc at baseline, 7 days after initiation, and periodically thereafter, as well as following dose adjustments

Approved by FDA on 10/29/07 (link to the FDA file). 

Tam CS et al. Failure to achieve a major cytogenetic response by 12 months defines inadequate response in patients receiving nilotinib or dasatinib as second or subsequent line therapy for chronic myeloid leukemia. Blood 2008; 112:516 (link to the article). 

Coutre PL et al. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia. Blood 2008; 111:1834 (link to the article).  

Giles F et al. A phase II study of nilotinib, a novel tyrosine kinase inhibitor administrated to patients with imatinib resistant or intolerant chronic myelogenous leukemia (CML) in chronic phase (CP), accelerated phase (AP) or blast crisis (BC) who have also failured dasatinib therapy. 2006 ASH annual meeting. Abstract 2170 (link to the abstract).

Kantarjian H et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Eng J Med 2006; 354:2542 (link to the article).


Chronic lymphocytic leukemia (back to top)

Chlorambucil
Chlorambucil (Leukeran)10 mg/m2/d po x 7 days or 40 mg/m2 po
Q4w x 12 cycles

Hillmen P et al. Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia. J Clin Oncol 2007; 25:5616 (link to the article). 

Catovsky D et al. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukemia (the LRF CLL4 trial): a randomized controlled trial. Lancet 2007; 370:230 (link to the article).  

Rai, KR et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med 2000; 343:1750 (link to the article).

Bendamustine
Bendamustine (Treanda) 100 mg/m2 iv over 30 min d1 and 2
Q4w x 6 cycles

Approved by FDA on 3/20/08 (link to FDA file)

Knauf W et al. Bendamustine versus chlorambucil in treatment-naive patients with B-cell chronic lymphocytic leukemia (B-CLL): results of an international phase III study. 2007 ASH annual meeting. Abstract 2043 (link to the abstract).   

Fludarabine
Fludarabine 25 mg/m2/d iv x 5 days or 40 mg/m2/d po x 5 days
Q4w x 6-12 cycles

Catovsky D et al. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukemia (the LRF CLL4 trial): a randomized controlled trial. Lancet 2007; 370:230 (link to the article). 

Rai, KR et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med 2000; 343:1750 (link to the article).

Cladribine
Cladribine (2-CdA)
Regimen 1
0.1 mg/kg/d civi d1-7 q4-5w

Saven A et al. 2-Chlorodeoxyadenosine activity in patients with untreated chronic lymphocytic leukemia. J Clin Oncol 1995; 13:570 (link to the article).

Regimen 2
0.12 mg/kg/d iv over 2 hrs d1-5 q4w x 6 cycles

Robak T et al. Cladribine alone and in combination with cyclophosphamide or cyclophosphamide plus mitoxantrone in the treatment of progressive chronic lymphocytic leukemia: report of a prospective, multicenter, randomized trial of the Polish Adult Leukemia Group (PALG CLL2). Blood 2006; 108:473 (link to the article). 

Rituximab
Rituximab (Rituxan) 375 mg/m2 iv qw x 4 wks q6m x 4 courses

Hainsworth, JD et al. Single-agent rituximab as first-line and maintenance treatment for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma: A phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 2003; 21:1746 (link to the article).

Alemtuzumab IV
Premedications:
Diphenhydramine (Benadryl) 50 mg po
Acetaminophen (Tylenol) 500-1000 mg po
Alemtuzumab (Campath) start at 3 mg/d iv, increase to 10 mg/d and 30 mg/d as soon as tolerated, then 30 mg/d iv over 2 hours tiw up to 12-16 weeks
Bactrim DS 1 tab po bid tiw
Famciclovir 250 mg po bid

Approved by FDA on 9/19/07 (link to FDA file). 

Hillmen P et al. Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia. J Clin Oncol 2007; 25:5616 (link to the article).

Keating, MJ et al. Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood 2002; 99:3554 (link to the article).

Rai, KR et al. Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine. J Clin Oncol 2002; 20:3891 (link to the article).

Alemtuzumab (Campath) SC +/- Fludarabine
Alemtuzumab (Campath) 30 mg/d sc tiw (after dose escalation in first week) x 24 wks
Add Fludarabine 40 mg/m2/d po for 3 days q4w for patients failing to response to alemtuzumab
Acyclovir and cotrimoxazole prophylaxis

Sayala HA et al. Final report of the UKCLL02 trial: a phase II study of subcutaneous alemtuzumab plus fludarabine in patients with fludarabine-refractory CLL (on behalf of the NCRI CLL trials subgroup). 2006 ASH annual meeting. Abstract 34 (link to the abstract). 

Chlorambucil + Prednisone
Chlorambucil (Leukeran) 30 mg/m2 po d1
Prednisone 80 mg po qd d1-5
Q2w

Raphael B et al. Comparison of chlorambucil and prednisone versus cyclophosphamide, vincristine, and prednisone as initial treatment for chronic lymphocytic leukemia: long-term follow-up of an Eastern Cooperative Oncology Group randomized clinical trial. J Clin Oncol 1991; 9:770 (link to the article).

Fludarabine + Prednisone
Fludarabine 30 mg/m2/d iv d1-5
Prednisone 30 mg/m2/d po d1-5
Q4w

O’Brien S et al. Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivarient analysis-derived prognostic model for response to treatment. Blood 1993; 82:1695 (link to the article).

Fludarabine + Cyclophosphamide (FC)
IV regimen 1
Fludarabine 25-30 mg/m2/d iv d1-3
Cyclophosphamide (Cytoxan) 250 mg/m2/d iv d1-3
Q4w x 6 cycles

Catovsky D et al. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukemia (the LRF CLL4 trial): a randomized controlled trial. Lancet 2007; 370:230 (link to the article). 

Eichhorst BF et al. Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy  of younger patients with chronic lymphocytic leukemia. Blood 2006; 107:885 (link to the article).

IV regimen 2
Fludarabine 20 mg/m2/d iv d1-5
Cyclophosphamide (Cytoxan) 600 mg/m2 iv d1
Q4w x 6 cycles

Flinn IW et al. Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997. J Clin Oncol 2007; 25:793 (link to the article). 

PO regimen
Fludarabine 24 mg/m2/d po d1-5
Cyclophosphamide (Cytoxan) 150 mg/m2/d po d1-5
Q4w x 6 cycles

Catovsky D et al. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukemia (the LRF CLL4 trial): a randomized controlled trial. Lancet 2007; 370:230 (link to the article).

Fludarabine + Rituximab
Fludarabine 25 mg/m2/d iv d1-5
Rituximab (Rituxan) 375 mg/m2 iv d1 and 4 of cycle 1, then d1 only for cycles 2-6
Q4w x 6 cycles
2 months later:
Rituximab (Rituxan) 375 mg/m2 iv qw x 4 doses

Byrd JC et al. Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B9712. Blood 2003; 101:6 (link to the article). 

Byrd, JC et al. Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: an updated retrospective comparative analysis of CALGB 9712 and CALGB 9011. Blood 2005; 105:49 (link to the article).

Fludarabine + Cyclophosphamide + Rituximab (FCR)
Fludarabine 25 mg/m2/d iv d1-3
Cyclophosphamide (Cytoxan) 250 mg/m2/d iv d1-3
Rituximab (Rituxan) 375 mg/m2 iv d1 cycle 1 and 500 mg/m2 iv d1 cycle 2-6
Q4w x 6 cycles
Allopurinol 300 mg po qd d1-7 cycle 1
Bactrim DS 1 po bid twice a week
Valacyclovir 500 mg po qd

Tam CS et al.  Seventy percent of complete responders remain in continuous remission: five-year follow-up of 300 patients treated with fludarabine, cyclophosphamide, and rituximab (FCR) as initial therapy of CLL. 2007 ASCO annual meeting. Abstract 7008 (link to the abstract).

Keating M et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for CLL. J Clin Oncol 2005; 22:4079 (link to the article). 

Cladribine + Mitoxantrone + Cyclophosphamide (CMC)
Cladribine (2-CdA) 0.12 mg/kg/d iv over 2 hrs d1-3
Mitoxantrone (Novantrone) 10 mg/m2 iv d1
Cyclophosphamide (Cytoxan) 650 mg/m2 iv d1
Q4w x 6 cycles

Robak T et al. Cladribine alone and in combination with cyclophosphamide or cyclophosphamide plus mitoxantrone in the treatment of progressive chronic lymphocytic leukemia: report of a prospective, multicenter, randomized trial of the Polish Adult Leukemia Group (PALG CLL2). Blood 2006; 108:473 (link to the article).

CVP
Cyclophosphamide (Cytoxan) 300 mg/m2/d po d1-5
Vincristine 1.4 mg/m2 (max 2 mg) iv d1
Prednisone 100 mg/m2/d po d1-5
Q3w up to 18 months

Raphael B et al. Comparison of chlorambucil and prednisone versus cyclophosphamide, vincristine, and prednisone as initial treatment for chronic lymphocytic leukemia: long-term follow-up of an Eastern Cooperative Oncology Group randomized clinical trial. J Clin Oncol 1991; 9:770 (link to the article).

Lenalidomide 
Regimen 1
Lenalidomide (Revlimid) 5 mg po qd, escalate by 5 mg every 1-2 weeks to 25 mg po qd d1-21 q4w until molecular CR or unacceptable toxicity
Allopurinol 300 mg po qd for 14 days starting 2-3 days before lenalidomide

Chanan-Khan A et al. Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: Results of a phase II study. J Clin Oncol 2006; 24:5343 (link to the article). 

Regimen 2
Lenalidomide (Revlimid) 10 mg po qd for 28 days, then increase by 5 mg every 28 days to 25 mg qd until progression or unacceptable toxicity

Ferrajoli A et al. Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia. Blood 2008; 111:5291 (link to the article). 

Lenalidomide + Rituximab
Lenalidomide (Revlimid) 25 mg po qd d1-21
Rituximab (Rituxan) 375 mg/m2 iv d1, 8 and 15 of cycle 1, then d1 and 15 of cycles 2-6
Q4w

Chanan-Khan A et al. Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: Results of a phase II study. J Clin Oncol 2006; 24:5343 (link to the article). 

Pentostatin + Cyclophosphamide + Rituximab (PCR)
Regimen 1
Pentostatin 2 mg/m2 iv d1 cycles 1-6
Cyclophosphamide (Cytoxan) 600 mg/m2 iv d1 cycles 1-6
Rituximab (Rituxan) 100 mg/m2 iv d1 and 375 mg/m2 d3 and 5 for cycle 1, then 375 mg/m2 d1 for cycles 2-6
Q3w x 6 cycles
Allopurinol 300 mg po qd d1-15 cycle 1
Filgrastim (Neupogen) support
Bactrim DS 1 po bid tiw x 1 year
Acyclovir 800 mg po bid x 1 year

Shanafelt TD et al. The pentostatin, cyclophosphamide, and rituximab regimen (PCR) is highly active and well tolerated regardless of patient age, creatinine clearance, and performance status: analysis of a multi-center phase II trial. 2006 ASH annual meeting. Abstract 36 (link to the abstract). 

Kay NE et al. Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia. Blood 2007; 109:405 (link to the article).

Regimen 2
Pentostatin 4 mg/m2 iv d1 cycles 1-6
Cyclophosphamide (Cytoxan) 600 mg/m2 iv d1 cycles 1-6
Rituximab (Rituxan) 375 mg/m2 iv d1 cycles 2-6
Q3w x 6 cycles
Filgrastim (Neupogen) support
Bactrim DS 1 po bid tiw
Acyclovir 800 mg po bid

Lamanna N et al. Pentostatin, cyclophosphamide, and rituximab is an active, well-tolerated regimen for patients with previously treated chronic lymphocytic leukemia.  J Clin Oncol 2006; 24:1575 (link to the article).

Cyclophosphamide + Fludarabine + Alemtuzumab + Rituximab (CFAR)
Cyclophosphamide (Cytoxan) 250 mg/m2/d iv d3-5
Fludarabine 25 mg/m2/d iv d3-5
Alemtuzumab (Campath) 30 mg iv d1, 3 and 5
Rituximab (Rituxan) 375-500 mg/m2 iv d2
Q4w x 6 cycles
Allopurinol 300 mg po qd d1-7 cycle 1
Pegfilgrastim (Neulasta) support
Bactrim DS 1 po bid tiw till 2 months after chemoimmunotherapy
Valganciclovir till 2 months after chemoimmunotherapy

Wierda WG et al. Combined cyclophosphamide, fludarabine, alemtuzumab, and rituximab (CFAR), an active regimen for heavily pretreated patients with CLL. 2006 ASH annual meeting. Abstract 31 (link to the abstract). 


Hairy cell leukemia (back to top)

Cladribine
Cladribine (2-CdA) 0.1 mg/kg/d civi d1-7

Chadha P et al. Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA): long-term follow-up of the Northwestern University experience. Blood 2005; 106:241 (link to the article).

Pentostatin
Pentostatin 4 mg/m2 iv
Q2w x 6 cycles

Cassileth PA et al. Pentostatin induces durable remission in hairy cell leukemia. J Clin Oncol 1991; 9:243 (link to the article).