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LEUKEMIA: CHRONIC 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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CML:Hydroxyurea (Hehlmann R, et al. Blood. 1994;84:4064-77)
N = 194
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CML:Hydroxyurea 40 mg/kg/d PO |
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Cytopenias* Mild Nausea* Dermatologic* Drug Fever*
*common toxicity, frequency not reported |
Daily― level 1 |
Treatment discontinued due to toxicity in < 1% of patients |
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CML:Interferon (Guilhot F, et al. N Engl J Med. 1997;337:223-29)
N = 361 |
CML:Interferon 5 MU/m2 SQ daily
Note: Decrease dose by 50% for granulocyte count < 1500/mm3 and/or platelets<100000/mm3 |
Hematologic toxicity (other) 2.5% |
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Nausea/vomiting/ Diarrhea 3.8% Mucositis 1% Other GI 1% Weight Loss/Asthenia 5.5% Skin Rash 2% Fever, Flu-like syndrome 2% Peripheral Neuropathy 1% Central Neurologic Syndrome 1% Depression 5.8% Other Psychologic 5.3% Cytolytic Hepatic 1% Other Toxicity 8.8% Thrombocytopenia 2.2% |
Level 1 |
97 patients discontinued therapy due to toxicity 42 deaths―mostly related to allogeneic or autologous BMT or disease progression |
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Interferon Cytarabine (Guilhot F, et al. N Engl J Med. 1997;337:223-29)
N = 360
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Interferon 5 MU/m2 SQ daily Cytarabine 20 mg/m2/d SQ days 1-10 every month
Note: Decrease dose by 50% for granulocyte count < 1500/mm3 and/or platelets < 100,000/mm3. Cytarabine held for WBC < 3000/mm3 and platelets < 100,000/mm3; cytarabine discontinued for granulocyte count < 1000/mm3 and platelets < 50,000/mm3. If hematologic control is not achieved, then increase cytarabine to 40 mg/m2/d SQ days 1-15. |
Hematologic toxicity (other) 8.6%
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Nausea/Vomiting/ Diarrhea 12.5% Mucositis 5.8% Other GI 1% Weight Loss/ Asthenia 13.3% Skin Rash 5.2% Fever, Flu-like Syndrome 3% Depression 4.2% other psychologic 3.6% Cytologic Hepatitis 2.5% Other Toxicity 8.6% Thrombocytopenia 5.5% |
Level 1 |
94 patiwnts discontinued therapy due to toxicity deaths―monstly related to allogeneic or autologous BMT or disease progression |
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LEUKEMIA: CHRONIC 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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STI-571/Imatinib mesylate (kantarjian H, et al. N Engl J Med. 2002;346:645-52)
N = 532 |
Chronic Phase Imatinib mesylate 400 mg orally daily
Note: The dose was increased to 400 mg orally twice daily in those in whom a complete hematologic response was not achieved after 3 month of treatment; in those whose disease relapsed within 3 month after the achievement of a complete hematologic response; and in those in whom a major cytogenetic response had not been achieved after 12 months of therapy. |
Neutropenia Grade III 27% Grade IV 8.1% Leukopenia Grade III 22% Grade IV 1.7% |
Grade III 6% Grade IV 1.1% |
Febrile Neutropenia 0.75%* Thrombocytopenia 20% Muscle cramps 0.9% Rash and Related Events 3% Nausea 1.5% Vomiting 0.6% Diarrhea 0.9% Superficial Edema 1.1% Weight Gain 4.3% Arthralgia 0.8% Fatigue 0.4% *Grade unknown, classified as serious drug-related adverse event |
Level 2 |
Median time to first Grade III or Grade IV episode of neutropenia was 62 days Drug-related adverse events led to treatment discontinuation in 11 (2.1%) patients |
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STI-571/Imatinib mesylate (Sawyers CL, et al. Blood. 2002;99:3530-39)
N = 260 |
Blast crisis Imarinib 400 mg or 600 mg orally daily (administered once a day with a meal)
Note: Starting dose increased to 600 mg orally daily after first 37 patients; dose was permitted to be Increased to a maximum of 400 mg orally twice daily in patients who relapsed, and in patients who did not achieve a hematologic response after at least 1 month of treatment. |
Neutropenia Grade III (400 mg) 14% Grade III ( 600 mg) 16% Grade IV (400 mg) 54% Grade IV (600 mg) 47% |
Grade III (400 mg) 43% Grade III (600 mg) 40% Grade IV (400 mg) 16% Grade IV (600 mg) 10% |
Thrombocytopenia 62% Hyperbilirubinemia (Grade III) 4% Transaminases: AST (Grade III) 2% ALT (Grade III) 2% Nausea 2% Vomiting 1% Diarrhea 0.8% Hemorrhage 2.3% Musuloskeletal pain < 1% Muscle Cramps < 1% Dermatitis/Rash 4% Fluid-Retention Events 6% Superficial Edema 3.5% Other Fluid-Retention Events 3.1% |
Level 3 |
Development of cytopenias dependent on stage of disease. with a frequency of Grade III-IV neutro- penia between 2 and 3 times higher in blast crisis and accelerated phase compared with chronic phase Hematologic side effects managed with a dose reduction or interruption (see prescribing information for recommendations) adverse events led to a temporary or perma- nent reduction in the initial dose of imatinib on one or more occa- sions in 46% of patients started on 400 mg daily and in 47% of patients started on 600 mg daily Drug-related adverse events leading to discontinuation to occurred in 5% of patients (all on 600 mg dose) |
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LEUKEMIA: CHRONIC MYELOGENOUS (continued ) : Page 3
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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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STI-571/Imatinib mesylate (Talpaz M, et al. Blood. 2002;99:1928-37)
N = 235 (400 mg = 77; 600 mg = 158) |
Accelerated Phase Imatinib 400 mg or 600 mg orally daily (administered once a day with a meal)
Note: Starting dose increased after first 77 patients; dose was able to be escalated to 400 mg orally twice daily in patients who had a relapse, or in those patients who did not achieve a hematologic response after at least 1 month of treatment.
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Neutropenia Grade III (400 mg) 21% Grade III (600 mg) 25% Grade IV (400 mg) 35% Grade IV (600 mg) 35% Leukopenia Grade III (400 mg) 27% Grade III (600 mg) 35% Grade IV (400 mg) 18% Grade IV (600 mg) 13% |
Grade III (400mg) 35% Grade III (600 mg) 32% Grade IV (400 mg) 9% Grade IV (600 mg) 15% |
Thrombocytopenia 43% Nausea 3% Vomiting 1% Fluid Retention 1 % Edema 3% Diarrhea 0.4% Hemorrhage 2% Transaminases (Grade III) AST 2% ALT 3% Hyperbilirubinemia (Grade III) 2% Dermatitis 1% Fatigue 3% Arthralgia 3%
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Level 3 |
Development of cytopenias dependent on stage of disease, with a frequency of Grade III-IV neutropenia between 2 and 3 times higher in blast crisis and accelerated phase compared with chronic phase Hematologic side effects managed with a dose reduction or interruption (see prescribing information for recommendations) Adverse events led to dose reduction in 49% of patients on 400 mg and 52% on 600 mg dose Adverse events leading to treatment discontinuation occurred in 2.5 % of patients (all in the 600 mg orally daily group ) 1 death suspected to be related to toxicity (liver failure) |