Table 6. Selected randomized studies... | American Society of Hematology

Table 6.

Selected randomized studies defining remission induction therapy in older adults.

Goal	Remission   Induction Agents	Complete  Remission	Overall Survival	Comments
Abbreviations: M, mitoxantrone; A, Ara-C (cytosine arabinoside); D, daunorubicin; I, idarubicin; E, etoposide; T, thioguanine; P, PSC-833; GM-CSF, granulocyte macrophage colony stimulating factor; G-CSF, granulocyte colony stimulating factor; ND, not done
¹ For comparison of DAT to ADE
² For comparison of DAT to MAC
³ For comparison of ADE to MAC
*Compare Anthracyclines and Anthracenediones*
Lowenberg, 1998²	M (8 mg/m²/d) +   A (100 mg/m²/d)   vs.   D (30 mg/m²/d) +   A (100 mg/m²/d)	47%  vs.  38%  P = 0.07	39 weeks (median)  9% (5 years)  vs.   36 weeks (median)  6% (5 years)   P = 0.23	Early and post-induction death rates   were similar for both arms. Patients  receiving mitoxantrone had a significantly  higher rate of severe infections (25.1%  vs 18.6%) and a trend toward a longer  duration of aplasia (22 vs 19 days).
AML Collaborative   Group, 1998¹⁹	I (8–20 mg/m²/d) +   A (100–200 mg/m²/d)   vs.   D (45–50 mg/m²/d) +   A (100–200 mg/m²/d)	51%   vs.  46%   P = ND	33.6 weeks (median)  vs.  29.9 weeks (median)  P = 0.58	Early induction failure tended to be higher   with idarubicin, while late induction failure   was lower. Myelosuppression was   greater in patients receiving idarubicin.
Archimbaud, 1999²⁰	I (8 mg/m²/d) +   A (100 mg/m²/d) +   E (100 mg/m²/d)   vs.   M (7 mg/m²/d) +   A (100–200 mg/m²/d)+   E (100 mg/m²/d)	45%  vs.  50%  P = 0.52	7 months (median)  21% (2 years)  vs.   7 months (median)  21% (2 years)  P = ND	No difference between groups in degree   of myelosuppression or in early death   rates.
*Vary 7+3 Dose*
Buchner, 1997²¹	D (60 mg/m²/d) +   A (100 mg/m²/d)   vs.   D (30 mg/m²/d) +   A (100 mg/m²/d)	54%  vs.   42%  P = 0.038	16% (5 years)  vs.   10% (5 years)   P = 0.11	The 30 mg daunorubicin arm was closed  prematurely due to higher response rates   in the 60 mg arm, resulting in 42 patients   receiving lower dose daunorubicin, and   130 patients receiving the higher dose.
Dillman, 1991¹³	D (45 mg/m²/d) +   A (100 mg/m²/d)   vs.   D (45 mg/m²/d) +   A (200 mg/m²/d)	44%  vs.   38%  P = 0.68	11.0 weeks (median)  vs.   9.6 weeks (median)  P = 0.23	This study has short overall survival times   compared to other studies in this patient   population.
*Add Agents*
Goldstone, 2001¹⁵	D (50 mg/m²/d) +   A (100 mg/m² q 12 hours)+   T (100 mg/m² q 12 hours)   vs.   D (50 mg/m²/d) +   A (100 mg/m² q 12 hours) +   E (100 mg/m²/d)   vs.   M (12 mg/m²/d) +   A (100 mg/m²/d	62%  vs.  50%  P = 0.002¹  vs.   55%  P = 0.04²	12% (5 years)  vs.  8% (5 years)  P = 0.02¹  vs.   10% (5 years)  P = 0.1,² 0.2³	There were no significant differences in  myelosuppression or other toxicities,   neutrophils were slower to recover in the  mitoxantrone arm. Patients receiving ADE  had higher rates of induction death (26%  compared to 16% for DAT and 17% for  MAC)
Baer, 2002⁵	D (60 mg/m²/d) +   A (100 mg/m²/d)+   E (100 mg/m²/d)   vs.   D (40 mg/m²/d) +   A (100 mg/m²/d) +   E (60 mg/m²/d) +   P (10 mg/kg/d)	46%  vs.   39%  P = 0.008	7 months (median)  vs.   2 months (median)  P = 0.48	Because of concern about excessive   mortality on the ADEP arm (25 deaths vs  12 on the ADE arm), it was closed early to  to further accrual. Survival between the  two arms was similar at one year.
*Use Hematopoietic Growth Factors*
Stone, 1995³	D (45 mg/m²/d) +   A (200 mg/m²/d)   vs.   D (45 mg/m²/d) +   A (200 mg/m²/d) +  GM-CSF (5 μg/kg/d)	54%  vs.   51%  P = 0.61	10.8 months   (median)  vs.   8.4 months  (median)  P = 0.10	Median duration of neutropenia was 15  days in the GM-CSF arm and 17 days in  placebo arm (P = 0.02). The duration of  hospitalization did not differ between the  arms; nor did the rates of life-threatening  infection, or persistent leukemia.
Godwin, 1998¹⁴	D (45 mg/m²/d) +   A (200 mg/m²/d)   vs.   D (45 mg/m²/d) +   A (200 mg/m²/d) +   G-CSF	50%  vs.   41%  P = 0.89	9 months  (median)  vs.   6 months   (median)  P = 0.71	The duration of neutropenia was 15%  shorter in the G-CSF arm compared to the  placebo arm (P = 0.14). The duration of   hospitalization did not differ between the  arms; nor did the rates of life-threatening  infection, or persistent leukemia.

Goal	Remission   Induction Agents	Complete  Remission	Overall Survival	Comments
Abbreviations: M, mitoxantrone; A, Ara-C (cytosine arabinoside); D, daunorubicin; I, idarubicin; E, etoposide; T, thioguanine; P, PSC-833; GM-CSF, granulocyte macrophage colony stimulating factor; G-CSF, granulocyte colony stimulating factor; ND, not done
¹ For comparison of DAT to ADE
² For comparison of DAT to MAC
³ For comparison of ADE to MAC
*Compare Anthracyclines and Anthracenediones*
Lowenberg, 1998²	M (8 mg/m²/d) +   A (100 mg/m²/d)   vs.   D (30 mg/m²/d) +   A (100 mg/m²/d)	47%  vs.  38%  P = 0.07	39 weeks (median)  9% (5 years)  vs.   36 weeks (median)  6% (5 years)   P = 0.23	Early and post-induction death rates   were similar for both arms. Patients  receiving mitoxantrone had a significantly  higher rate of severe infections (25.1%  vs 18.6%) and a trend toward a longer  duration of aplasia (22 vs 19 days).
AML Collaborative   Group, 1998¹⁹	I (8–20 mg/m²/d) +   A (100–200 mg/m²/d)   vs.   D (45–50 mg/m²/d) +   A (100–200 mg/m²/d)	51%   vs.  46%   P = ND	33.6 weeks (median)  vs.  29.9 weeks (median)  P = 0.58	Early induction failure tended to be higher   with idarubicin, while late induction failure   was lower. Myelosuppression was   greater in patients receiving idarubicin.
Archimbaud, 1999²⁰	I (8 mg/m²/d) +   A (100 mg/m²/d) +   E (100 mg/m²/d)   vs.   M (7 mg/m²/d) +   A (100–200 mg/m²/d)+   E (100 mg/m²/d)	45%  vs.  50%  P = 0.52	7 months (median)  21% (2 years)  vs.   7 months (median)  21% (2 years)  P = ND	No difference between groups in degree   of myelosuppression or in early death   rates.
*Vary 7+3 Dose*
Buchner, 1997²¹	D (60 mg/m²/d) +   A (100 mg/m²/d)   vs.   D (30 mg/m²/d) +   A (100 mg/m²/d)	54%  vs.   42%  P = 0.038	16% (5 years)  vs.   10% (5 years)   P = 0.11	The 30 mg daunorubicin arm was closed  prematurely due to higher response rates   in the 60 mg arm, resulting in 42 patients   receiving lower dose daunorubicin, and   130 patients receiving the higher dose.
Dillman, 1991¹³	D (45 mg/m²/d) +   A (100 mg/m²/d)   vs.   D (45 mg/m²/d) +   A (200 mg/m²/d)	44%  vs.   38%  P = 0.68	11.0 weeks (median)  vs.   9.6 weeks (median)  P = 0.23	This study has short overall survival times   compared to other studies in this patient   population.
*Add Agents*
Goldstone, 2001¹⁵	D (50 mg/m²/d) +   A (100 mg/m² q 12 hours)+   T (100 mg/m² q 12 hours)   vs.   D (50 mg/m²/d) +   A (100 mg/m² q 12 hours) +   E (100 mg/m²/d)   vs.   M (12 mg/m²/d) +   A (100 mg/m²/d	62%  vs.  50%  P = 0.002¹  vs.   55%  P = 0.04²	12% (5 years)  vs.  8% (5 years)  P = 0.02¹  vs.   10% (5 years)  P = 0.1,² 0.2³	There were no significant differences in  myelosuppression or other toxicities,   neutrophils were slower to recover in the  mitoxantrone arm. Patients receiving ADE  had higher rates of induction death (26%  compared to 16% for DAT and 17% for  MAC)
Baer, 2002⁵	D (60 mg/m²/d) +   A (100 mg/m²/d)+   E (100 mg/m²/d)   vs.   D (40 mg/m²/d) +   A (100 mg/m²/d) +   E (60 mg/m²/d) +   P (10 mg/kg/d)	46%  vs.   39%  P = 0.008	7 months (median)  vs.   2 months (median)  P = 0.48	Because of concern about excessive   mortality on the ADEP arm (25 deaths vs  12 on the ADE arm), it was closed early to  to further accrual. Survival between the  two arms was similar at one year.
*Use Hematopoietic Growth Factors*
Stone, 1995³	D (45 mg/m²/d) +   A (200 mg/m²/d)   vs.   D (45 mg/m²/d) +   A (200 mg/m²/d) +  GM-CSF (5 μg/kg/d)	54%  vs.   51%  P = 0.61	10.8 months   (median)  vs.   8.4 months  (median)  P = 0.10	Median duration of neutropenia was 15  days in the GM-CSF arm and 17 days in  placebo arm (P = 0.02). The duration of  hospitalization did not differ between the  arms; nor did the rates of life-threatening  infection, or persistent leukemia.
Godwin, 1998¹⁴	D (45 mg/m²/d) +   A (200 mg/m²/d)   vs.   D (45 mg/m²/d) +   A (200 mg/m²/d) +   G-CSF	50%  vs.   41%  P = 0.89	9 months  (median)  vs.   6 months   (median)  P = 0.71	The duration of neutropenia was 15%  shorter in the G-CSF arm compared to the  placebo arm (P = 0.14). The duration of   hospitalization did not differ between the  arms; nor did the rates of life-threatening  infection, or persistent leukemia.