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LEUKEMIA: ACUTE MYELOGENOUS
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Regimen/Number Of Patients |
Drug Dose and Route |
Leukopenia/ Neutropenia Toxicity |
Anemia Toxicity |
Other Grade III-IV Toxicities |
Emetogenic Potential |
Consequences of Adverse Event(s) |
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5+2* (Ral kr, et al. Blood. 1981;58:1203-12)
N = 75 |
Cytarabine 100 mg/m2/d IV continuous Infusion days 1-5 Daunorubicin 45 mg/m2/d IV days 1, 2 *For reinduction |
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Infection 51% Hemorrhage 20% Hepatic 7% Renal 5% Cardiac 4%
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Days 1, 2― level 4 Days 3-5― level 2
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Death due to therapy 32% Sepsis was the most common cause of death |
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CECA (Kornblau SM, et al. Leuk Lymphoma. 1998;28:371-75)
N = 25
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Cyclophosphamide 1000 mg/m2/d IV over 2 hours days 1-3 Etoposide 200 mg/m2/d IV over 3 hours days 1-3 Carboplatin 150 mg/m2/d for 3 days IV continuous Infusion days 1-3 Cytarabine 1000 mg/m2/d IV over 2 hours days 1-3
Note: Agents administered sequentially, with cyclophosphamide first, then etoposide, carboplatin, and finally cytarabine.
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Neutropenic Fever 76% Hyperbilirubinemia (Grade IV) 4% Hemorrhagic cystitis (Grade IV) 4% Diarrhea (Grade III) 4% Mucositis (Grade III) 4% Cardiac Toxicity (Grade III) 4% |
Days 1-3― level 5 |
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Cytarabine (Mayer RJ, et al. N Engl J Med. 1994;331:896-903)
N = 203 |
Cytarabine 100 mg/m2/d IV continuous Infusion days 1-5* Repeat cycle every 28 days or 1 week after marrow recovery *For patients > 60 years of age |
Grade III-IV > 16% |
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Patients Requiring Hospitalization Due to Neutropenic Fever 16% Patients Requiring Transfusions Due to Thrombocytopenia 28% |
Days 1-5― level 2
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1% of patients died while in remission 76% of patients tolerated full-dose therapy for 4 courses |
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EMA-86 (Archimbaud E, et al. J Clin Oncol. 1995;13:11-18)
N = 133 |
Mitoxantrone 12 mg/m2/d IV days 1-3 Cytarabine 500 mg/m2/d IV continuous Infusion days 1-3, 8-10 Etoposide 200 mg/m2/d IV continuous Infusion days 8-10
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100% |
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Neutropenic Infection* 54% Thrombocytopenia* 100% Mucositis* 23% Hyperbilirubinemia* 8% Bleeding* 6% Rash* 5% Diarrhea* 3% Metabolic Disorders* 2% Cerebellar Syndrome* 1% Vomiting* 9%
*WHO Grade > 2 toxicity |
Days 1-3― level 4 Days 8-10― level 3 |
Infection death 9% Median duration of neutropenia (Grade IV) 31 days of patients receiving a 2nd course, 5 patients (19%) died of toxicity (4 of infection, 1 of cerebral hemorrhage)
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LEUKEMIA: ACUTE MYELOGENOUS (continued ) : Page 2
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Regimen/Number Of Patients |
Drug Dose and Route |
Leukopenia/ Neutropenia Toxicity |
Anemia Toxicity |
Other Grade III-IV Toxicities |
Emetogenic Potential |
Consequences of Adverse Event(s) |
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FLAG (Montillo M, et al. AM J Hematol. 1998;58:105-109)
N = 38 |
Fludarabine 30 mg/m2/d IV over 30 minutes days 1-5 Cytarabine 2000 mg/m2/d IV over 4 hours after completion of fludarabine days 1-5 G-CSF 5 mcg/kg/d IV day 0 (24 hours prior to starting chemotherapy) until ANC recovery
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Neutropenia Grade IV 100% |
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Documented Infections (> Grade III) 44% Bacterial Infection 34% Fungal infection 10% Fever of unknown Origin 44% Mucositis (> Grade III) 10% Diarrhea (> Grade III) 8% Hepatic (> Grade III) 8% Neurologic (> Grade III)2% |
Days 1-5― level 4 |
Median time to ANC 500/mL was 21 days and to ANC > 1000/mL was 23 days Median time to platelet levels > 20,000 was 26 days and to platelets > 100,000 was 28 days Median time of G-CSF Administration was 21 days (range 17-61) Median time hospitalized Was 31 days (range 17-16) |
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HiDAC (Mayer RJ, et al. N Engl J Med. 1994;331:896-903)
N = 187 |
Cytarabine 3000 mg/m2 IV Over 3 hours every 12 hours Days1, 3, 5 (total 6 doses) Administer with saline, methylcellulose, or Steroid eye drops OU, every 6 hours, beginning with cytarabine and continuing 48-72 hours after the last cytarabine dose Repeat cycle every 28 days or 1 week after marrow recovery |
Grade III-IV 71% |
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Patients Requiring Hospitalization Due to Neutropenic Fever/Infection 71% Thrombocytopenia (Grade IV) 86% CNS Toxicities 12% (32% with age > 60 yrs) |
Days 1, 3, 5 ―level 4 |
5% of patients died while in remission patients hospitalized for neutropenic fever 71% 56% of patients tolerated 4 courses of therapy at full dose 86% of patients required platelet transfusions |
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(continued ) : Page 3 LEUKEMIA: ACUTE MYELOGENOUS, RELAPSED
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Regimen/Number Of Patients |
Drug Dose and Route |
Leukopenia/ Neutropenia Toxicity |
Anemia Toxicity |
Other Grade III-IV Toxicities |
Emetogenic Potential |
Consequences of Adverse Event(s) |
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Gemtuzumab ozogamicin (sievers EL, et al. J Clin Oncol. 2001;19:3244-54)
N = 142 |
Gemtuzumab 9 mg/m2 IV for up to 3 doses with at least 14 days, but not greater than days between doses Appropriate premedications listed in Section 2, Commonly Used Premedication Regimens |
Neutropenia Grade III-IV 97% |
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Infection 28% Sepsis 16% Pneumonia 7% Fever 15% Chills 13% Thrombocytopenia 99% Hypertension 9% Hypotension 8% Asthenia 7% Mucositis 4% Hyperbilirubinemia (Grade III) 23% (Grade IV) 1% Transaminases 17% Nausea/Vomiting 11% Dyspnea 9% |
Days 1, 14― level 3 |
Grade III-IV bleeding 15%, which included epistaxis (3%) and intracranial hemorrhage (4%) patients (13%) died during the treatment period: disease progression (8), multiorgan failure (4), CNS hemorrhage (5), sepsis (2) Incidence of infusion related symptoms was significantly lower after the second dose compared with the first dose (Grade III-IV 34% vs 12%) Hepatotoxicity, including severe veno-occlusive disease (VOD), has been reported in association with the use of gemtuzumab Median time to onset of Grade III-IV hyper. bilirubinemia was 8 days and the median duration was 20 days 1 patient died with liver failure in the setting of tumor lysis syndrome and multi- system organ failure 1 patient died after an episode of persistent ascites and hepatosplenomegaly |