Table 1.
Selected Randomized Trials of Induction Chemotherapy for Older Patients With AML
| Chemotherapy Regimen* | Year Published | Age Range (years) | No. of Patients | CR (%) | OS |
Induction Death Rate (%) | Comments | |
|---|---|---|---|---|---|---|---|---|
| Median (months) | P | |||||||
| Intensive v supportive care | ||||||||
| Löwenberg et al7 | 1989 | 65-85 | < .05 | No difference in days hospitalized | ||||
| Cytarabine, daunorubicin, and vincristine | 31 | 58 | 5.3 | 9.7 | ||||
| Supportive care | 29 | 0 | 2.8 | NA | ||||
| Type of anthracycline/dose intensification | ||||||||
| Löwenberg et al27 | 1998 | 61-88 | .23 | |||||
| Cytarabine plus daunomycin | 242 | 38 | 9.0 | 6.0 | ||||
| Cytarabine plus mitoxantrone | 247 | 47 | 9.7 | 6.0 | ||||
| Pautas et al29 | 2010 | 50-70 | No difference | .16 | Median OS of 17 months for entire study cohort | |||
| Cytarabine plus daunorubicin 80 mg/m2 | 156 | 70 | 8 | |||||
| Cytarabine plus idarubacin 12 mg/m2 × 3 days | 155 | 83 | 3 | |||||
| Cytarabine plus idarubacin 12 mg/m2 × 4 days | 157 | 78 | 6 | |||||
| Löwenberg et al33 | 2009 | 60-83 | No difference | .16 | OS benefits suggested in patients age 60-65 years | |||
| Cytarabine plus daunorubicin 45 mg/m2 | 411 | 54 | 11 | |||||
| Cytarabine plus daunorubicin 90 mg/m2 | 402 | 64 | 12 | |||||
| Dose-attenuated induction | ||||||||
| Tilly et al26 | 1990 | 65-83 | .12 | |||||
| Rubidazone plus cytarabine | 46 | 52 | 12.8 | 31 | ||||
| Low-dose cytarabine | 41 | 32 | 8.8 | 10 | ||||
| Growth factor support | ||||||||
| Stone et al31 | 1995 | 60-80† | .10 | |||||
| Cytarabine plus daunorubicin | 195 | 54 | 9.4 | 16 | ||||
| Cytarabine, daunorubicin, and GM-CSF | 193 | 51 | 9.4 | 20 | ||||
| MDR1 modulation | ||||||||
| Baer et al32 | 2002 | 60-84 | No difference | .48 | ||||
| Cytarabine, daunorubicin, and etoposide | 61 | 46 | 20 | |||||
| Cytarabine, daunorubicin, etoposide, and PSC-833 | 59 | 39 | 44 | |||||
| Addition of sorafenib | ||||||||
| Serve et al30 | 2013 | 61-80 | No difference | .88 | FLT3-ITD positive, 14% | |||
| Cytarabine plus daunorubicin 60 mg/m2 | 97 | 60 | 7 | |||||
| Cytarabine, daunorubicin 60 mg/m2, and sorafenib | 104 | 48 | 17 | |||||
| Addition of gemtuzumab ozogamicin | ||||||||
| Castaigne et al34 | 2012 | 50-70 | < .05 | |||||
| Cytarabine plus daunorubicin | 139 | 75‡ | 11 | 4 | ||||
| Cytarabine, daunorubicin, and gemtuzumab | 139 | 81‡ | 28 | 6 | ||||
| Burnett et al35 | 2012 | 51-84 | .05 | Improved 3-year survival: 25% v 20% | ||||
| Daunorubicin, cytarabine, or clofarabine | 556 | 58 | Improved | 9 | ||||
| Daunorubicin, cytarabine, or clofarabine plus gemtuzumab | 559 | 65 | 8 | |||||
| Lower-intensity therapy | ||||||||
| Kantarjian et al36 | 2012 | 64-91 | .2 | Poor- or intermediate-risk cytogenetics only; ECOG PS 0-2 with minimal comorbid conditions | ||||
| Supportive care or low-dose cytarabine | 243 | 8 | 5 | 8 | ||||
| Decitabine | 242 | 18 | 8 | 9 | ||||
| Burnett et al37 | 2007 | 51-90 | < .05 | No specific fitness criteria except comorbidity if age < 70 years | ||||
| Low-dose cytarabine ± ATRA | 103 | 18 | Improved | 26 | ||||
| Hydroxyurea ± ATRA | 99 | 1 | 26 | |||||
| Burnett et al38 | 2013 | 51-90 | No difference | .7 | ||||
| Clofarabine | 200 | 22 | 18 | |||||
| Low-dose cytarabine | 206 | 12 | 13 | |||||
Abbreviations: AML, acute myelogenous leukemia; ATRA, all-trans-retinoic acid; CR, complete remission; ECOG, Eastern Cooperative Oncology Group; GM-CSF, granulocyte macrophage colony-stimulating growth factor; NA, not applicable; OS, overall survival; PS, performance status.
One limitation in translating clinical trial data into best practice is lack of consistency in patient populations recruited and in drug doses used, making comparisons of results between trials challenging. To date, there are no older patient–specific dosing recommendations for many drugs based on physiologic changes of aging beyond adjustments for creatinine clearance when appropriate, cardiac function (ie, anthracyclines), and unacceptable toxicity risk (ie, high-dose cytarabine).
Age ≥ 80 years, 4%.
Rates represent CR with incomplete platelet count recovery.