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result sql = Phase II study of SU5416--a small-molecule, vascular endothelial growth factor tyrosine-kinase receptor inhibitor--in patients with refractory myeloproliferative diseases.
Phase II study of SU5416--a small-molecule, vascular endothelial growth factor tyrosine-kinase receptor inhibitor--in patients with refractory myeloproliferative diseases.
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char = d;code = 100
char = y;code = 121
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char = <;code = 60
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char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = T;code = 84
char = h;code = 104
char = i;code = 105
char = r;code = 114
char = t;code = 116
char = y;code = 121
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char = t;code = 116
char = w;code = 119
char = o;code = 111
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
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char = 1;code = 49
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char = p;code = 112
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char = i;code = 105
char = e;code = 101
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char = t;code = 116
char = s;code = 115
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = B;code = 66
char = C;code = 67
char = R;code = 82
char = -;code = 45
char = A;code = 65
char = B;code = 66
char = L;code = 76
char = ;code = 32
char = n;code = 110
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char = g;code = 103
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
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char = M;code = 77
char = P;code = 80
char = D;code = 68
char = ,;code = 44
char = ;code = 32
char = 6;code = 54
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char = p;code = 112
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = e;code = 101
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char = t;code = 116
char = s;code = 115
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = C;code = 67
char = M;code = 77
char = M;code = 77
char = L;code = 76
char = ,;code = 44
char = ;code = 32
char = 4;code = 52
char = ;code = 32
char = p;code = 112
char = a;code = 97
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char = i;code = 105
char = e;code = 101
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char = t;code = 116
char = s;code = 115
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = C;code = 67
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char = L;code = 76
char = -;code = 45
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char = P;code = 80
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 3;code = 51
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char = p;code = 112
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = A;code = 65
char = M;code = 77
char = M;code = 77
char = );code = 41
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 6;code = 54
char = 6;code = 54
char = ;code = 32
char = y;code = 121
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = 2;code = 50
char = 9;code = 57
char = -;code = 45
char = 8;code = 56
char = 5;code = 53
char = ;code = 32
char = y;code = 121
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = s;code = 115
char = );code = 41
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = S;code = 83
char = U;code = 85
char = 5;code = 53
char = 4;code = 52
char = 1;code = 49
char = 6;code = 54
char = ;code = 32
char = 1;code = 49
char = 4;code = 52
char = 5;code = 53
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = /;code = 47
char = m;code = 109
char = (;code = 40
char = 2;code = 50
char = );code = 41
char = ;code = 32
char = t;code = 116
char = w;code = 119
char = i;code = 105
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = k;code = 107
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = a;code = 97
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char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = ;code = 32
char = 4;code = 52
char = -;code = 45
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = k;code = 107
char = ;code = 32
char = c;code = 99
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char = c;code = 99
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = m;code = 109
char = a;code = 97
char = x;code = 120
char = i;code = 105
char = m;code = 109
char = u;code = 117
char = m;code = 109
char = ,;code = 44
char = ;code = 32
char = 1;code = 49
char = 2;code = 50
char = ;code = 32
char = c;code = 99
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char = c;code = 99
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = );code = 41
char = .;code = 46
char = ;code = 32
char = D;code = 68
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = G;code = 71
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = 3;code = 51
char = -;code = 45
char = 4;code = 52
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = u;code = 117
char = t;code = 116
char = e;code = 101
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char = a;code = 97
char = b;code = 98
char = d;code = 100
char = o;code = 111
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char = a;code = 97
char = l;code = 108
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char = p;code = 112
char = a;code = 97
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char = n;code = 110
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char = 1;code = 49
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char = %;code = 37
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char = ,;code = 44
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char = b;code = 98
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char = e;code = 101
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char = p;code = 112
char = a;code = 97
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char = n;code = 110
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char = (;code = 40
char = 9;code = 57
char = %;code = 37
char = );code = 41
char = ,;code = 44
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char = i;code = 105
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char = u;code = 117
char = s;code = 115
char = i;code = 105
char = o;code = 111
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char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = d;code = 100
char = y;code = 121
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char = e;code = 101
char = a;code = 97
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char = (;code = 40
char = 9;code = 57
char = %;code = 37
char = );code = 41
char = ;code = 32
char = o;code = 111
char = r;code = 114
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char = h;code = 104
char = e;code = 101
char = a;code = 97
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char = a;code = 97
char = c;code = 99
char = h;code = 104
char = e;code = 101
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char = 6;code = 54
char = %;code = 37
char = );code = 41
char = ,;code = 44
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char = f;code = 102
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = g;code = 103
char = u;code = 117
char = e;code = 101
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char = 6;code = 54
char = %;code = 37
char = );code = 41
char = ,;code = 44
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char = a;code = 97
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char = r;code = 114
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char = e;code = 101
char = a;code = 97
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char = (;code = 40
char = 3;code = 51
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char = );code = 41
char = ,;code = 44
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char = a;code = 97
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char = d;code = 100
char = ;code = 32
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char = e;code = 101
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char = e;code = 101
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char = s;code = 115
char = i;code = 105
char = t;code = 116
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char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = t;code = 116
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char = o;code = 111
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char = s;code = 115
char = ;code = 32
char = (;code = 40
char = 3;code = 51
char = %;code = 37
char = );code = 41
char = .;code = 46
char = ;code = 32
char = E;code = 69
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = n;code = 110
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char = p;code = 112
char = a;code = 97
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char = i;code = 105
char = e;code = 101
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char = t;code = 116
char = s;code = 115
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char = %;code = 37
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char = e;code = 101
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char = a;code = 97
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char = (;code = 40
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char = p;code = 112
char = a;code = 97
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char = i;code = 105
char = e;code = 101
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char = s;code = 115
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char = h;code = 104
char = a;code = 97
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char = r;code = 114
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char = r;code = 114
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char = s;code = 115
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char = e;code = 101
char = a;code = 97
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char = e;code = 101
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char = ;code = 32
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char = b;code = 98
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char = c;code = 99
char = a;code = 97
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char = s;code = 115
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char = ;code = 32
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char = t;code = 116
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char = M;code = 77
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char = E;code = 69
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char = f;code = 102
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char = <;code = 60
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char = >;code = 62
char = <;code = 60
char = b;code = 98
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char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = S;code = 83
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char = :;code = 58
char = ;code = 32
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char = /;code = 47
char = b;code = 98
char = >;code = 62
char = S;code = 83
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char = 5;code = 53
char = 4;code = 52
char = 1;code = 49
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char = w;code = 119
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char = h;code = 104
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char = M;code = 77
char = P;code = 80
char = D;code = 68
char = .;code = 46
char = ;code = 32
char = L;code = 76
char = o;code = 111
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char = g;code = 103
char = -;code = 45
char = t;code = 116
char = e;code = 101
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char = s;code = 115
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char = a;code = 97
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char = f;code = 102
char = ;code = 32
char = a;code = 97
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char = t;code = 116
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result sql = BACKGROUND : Increased bone marrow angiogenesis and vascular endothelial growth factor (VEGF) levels are of adverse prognostic significance in patients with myeloproliferative disorders (MPD), including agnogenic myeloid metaplasia (AMM), chronic myeloid leukemia in blastic phase (CML-BP), and chronic myelomonocytic leukemia (CMML). VEGF is a soluble, circulating, angiogenic molecule that acts through receptor tyrosine kinases (RTK), including VEGF receptor 2 (VEGFR-2). SU5416 is a small-molecule RTK inhibitor (RTKI) that targets VEGFR-2, c-kit, and fms-related tyrosine kinase Flk2.

METHODS : Adult patients with advanced CMML, AMM, CML-BP, or other BCR-ABL negative MPD were entered on a multicenter, Phase II study.

RESULTS : Thirty-two patients (19 patients with BCR-ABL negative MPD, 6 patients with CMML, 4 patients with CML-BP, and 3 patients with AMM) with a median age of 66 years (range, 29-85 years) received SU5416 145 mg/m(2) twice weekly intravenously for a median of three 4-week cycles (maximum, 12 cycles). Drug-related Grade 3-4 toxicities included acute abdominal pain (13%), bone pain (9%), infusion-related dyspnea (9%) or headache (6%), fatigue (6%), diarrhea (3%), and catheter site reactions (3%). Eleven patients (34%) did not receive a second cycle of therapy (6 patients had progressive disease, 3 because of adverse events; 2 patients withdrew due to lack of response). One patient with AMM achieved a partial response. Eight patients received more than 6 months of therapy.

CONCLUSIONS : SU5416 had minimal clinical activity in patients with MPD. Long-term administration of a twice-weekly, hyperosmolar, intravenous solution containing polyoxyl 35 castor oil was difficult. More tolerable RTKI may be worthy of further investigation in patients with MPD.

Publication: Cancer 2003 Apr 15 ;97(8)::1920-8.
Publication Date: 2003 Apr 15
Study Author(s): Giles, Francis J;Cooper, Maureen A;Silverman, Lewis;Karp, Judith E;Lancet, Jeffrey E;Zangari, Maurizio;Shami, Paul J;Khan, Khuda D;Hannah, Alison L;Cherrington, Julie M;Thomas, Deborah A;Garcia-Manero, Guillermo;Albitar, Maher;Kantarjian, Hagop M;Stopeck, Alison T;
Institution: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. [email protected]
Shortcut link to this study:
BACKGROUND : Increased bone marrow angiogenesis and vascular endothelial growth factor (VEGF) levels are of adverse prognostic significance in patients with myeloproliferative disorders (MPD), including agnogenic myeloid metaplasia (AMM), chronic myeloid leukemia in blastic phase (CML-BP), and chronic myelomonocytic leukemia (CMML). VEGF is a soluble, circulating, angiogenic molecule that acts through receptor tyrosine kinases (RTK), including VEGF receptor 2 (VEGFR-2). SU5416 is a small-molecule RTK inhibitor (RTKI) that targets VEGFR-2, c-kit, and fms-related tyrosine kinase Flk2.

METHODS : Adult patients with advanced CMML, AMM, CML-BP, or other BCR-ABL negative MPD were entered on a multicenter, Phase II study.

RESULTS : Thirty-two patients (19 patients with BCR-ABL negative MPD, 6 patients with CMML, 4 patients with CML-BP, and 3 patients with AMM) with a median age of 66 years (range, 29-85 years) received SU5416 145 mg/m(2) twice weekly intravenously for a median of three 4-week cycles (maximum, 12 cycles). Drug-related Grade 3-4 toxicities included acute abdominal pain (13%), bone pain (9%), infusion-related dyspnea (9%) or headache (6%), fatigue (6%), diarrhea (3%), and catheter site reactions (3%). Eleven patients (34%) did not receive a second cycle of therapy (6 patients had progressive disease, 3 because of adverse events; 2 patients withdrew due to lack of response). One patient with AMM achieved a partial response. Eight patients received more than 6 months of therapy.

CONCLUSIONS : SU5416 had minimal clinical activity in patients with MPD. Long-term administration of a twice-weekly, hyperosmolar, intravenous solution containing polyoxyl 35 castor oil was difficult. More tolerable RTKI may be worthy of further investigation in patients with MPD.
PMID: 12673719

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