7 0 22 0.2
Asthenia 18 5 21 5 15 0.2
Dyspnea 15 4 21 7 12 0.9
Upper Respiratory Tract Infection 3 0 12 0.4 19 0
Anorexia 14 2 17 2 7 0
Night Sweats 13 0.8 17 1 14 0.2
Constipation 16 2 16 0.9 9 0.4
Dizziness 12 0.4 13 0 16 0.2
Pharyngitis 10 0 12 0 15 0
Insomnia 10 0 14 0 14 0.2
Pruritus 8 1 14 0.9 14 0.8
Hypokalemia 13 4 9 2 6 0.8
Pneumonia 13 7 10 7 4 1
Anxiety 8 0.8 12 0 8 0.4
Liver Toxicity 10 5 12 6 6 3
Rigors 10 0 12 0.4 10 0
Chest Pain 7 2 10 0.4 11 0.8
Influenza 0.8 0.4 6 0 11 0.2
Sinusitis 4 0.4 11 0.4 9 0.4
(1) All adverse reactions occurring in ≥10% of patients are listed regardless of suspected relationship to treatment.
(2) Other fluid retention reactions include pleural effusion, ascites, pulmonary edema, pericardial effusion, anasarca, edema aggravated, and fluid retention not otherwise specified.
6.2 Hematologic ToxicityCytopenias, and particularly neutropenia and thrombocytopenia, were a consistent finding in all studies, with a higher frequency at doses ≥750 mg (Phase 1 study). The occurrence of cytopenias in CML patients was also dependent on the stage of the disease.
In patients with newly diagnosed CML, cytopenias were less frequent than in the other CML patients (see Tables 4 and 5). The frequency of Grade 3 or 4 neutropenia and thrombocytopenia was between 2- and 3-fold higher in blast crisis and accelerated phase compared to chronic phase (see Tables 4 and 5). The median duration of the neutropenic and thrombocytopenic episodes varied from 2 to 3 weeks, and from 2 to 4 weeks, respectively.
These reactions can usually be managed with either a reduction of the dose or an interruption of treatment with Gleevec, but in rare cases require permanent discontinuation of treatment.
Table 4Lab Abnormalities in Newly Diagnosed CML Clinical Trial Gleevec
N=551 IFN+Ara−C
N=533
% %
CTC Grades Grade 3 Grade 4 Grade 3 Grade 4
Hematology Parameters*
− Neutropenia* 13.1 3.6 20.8 4.5
− Thrombocytopenia* 8.5 0.4 15.9 0.6
− Anemia 3.3 1.1 4.1 0.2
Biochemistry Parameters
− Elevated Creatinine 0 0 0.4 0
− Elevated Bilirubin 0.9 0.2 0.2 0
− Elevated Alkaline Phosphatase 0.2 0 0.8 0
− Elevated SGOT /SGPT 4.7 0.5 7.1 0.4
*p<0.001 (difference in Grade 3 plus 4 abnormalities between the two treatment groups)
Table 5Lab Abnormalities in Other CML Clinical Trials Myeloid Blast Crisis
(n=260) Accelerated Phase
(n=235) Chronic Phase, IFN Failure
(n=532)
600 mg n=223
400 mg n=37 600 mg n=158
400 mg n=77 400 mg
% % %
CTC Grades1 Grade 3 Grade 4 Grade 3 Grade 4 Grade 3 Grade 4
Hematology Parameters
− Neutropenia 16 48 23 36 27 9
− Thrombocytopenia 30 33 31 13 21 <1
− Anemia 42 11 34 7 6 1
Biochemistry Parameters
− Elevated Creatinine 1.5 0 1.3 0 0.2 0
− Elevated Bilirubin 3.8 0 2.1 0 0.6 0
− Elevated Alkaline Phosphatase 4.6 0 5.5 0.4 0.2 0
− Elevated SGOT (AST) 1.9 0 3.0 0 2.3 0
− Elevated SGPT (ALT) 2.3 0.4 4.3 0 2.1 0
1CTC Grades: neutropenia (Grade 3 ≥0.5-1.0 x 109/L, Grade 4 <0.5 x 109/L), thrombocytopenia (Grade 3 ≥10-50 x 109/L, Grade 4 <10 x 109/L), anemia (hemoglobin ≥65-80 g/L, Grade 4 <65 g/L), elevated creatinine (Grade 3 >3-6 x upper limit normal range [ULN], G
