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result sql = A phase I study of induction chemotherapy for older patients with newly diagnosed acute myeloid leukemia (AML) using mitoxantrone, etoposide, and the MDR modulator PSC 833: a southwest oncology group study 9617.
A phase I study of induction chemotherapy for older patients with newly diagnosed acute myeloid leukemia (AML) using mitoxantrone, etoposide, and the MDR modulator PSC 833: a southwest oncology group study 9617.char = O;code = 79
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result sql = Older patients with acute myelogenous leukemia (AML) have overexpression of P-glycoprotein (Pgp+), and this has been shown to correlate quantitatively with therapeutic outcome. Since Pgp-mediated efflux of cytotoxic drugs can be inhibited by the cyclosporine analogue, PSC 833, we investigated the use of this agent with a 5-day mitoxantrone/etoposide regimen in patients over age 55 with newly diagnosed AML. Previous studies suggested a 33% incidence of grade IV/V non-hematologic toxicity with the use of mitoxantrone 10 mg/M(2) and etoposide 100 mg/M(2), each for 5 days, in this patient population. Since PSC 833 alters the pharmacokinetic excretion of MDR-related cytotoxins, this phase I dose-finding study was performed to identify doses of mitoxantrone/etoposide associated with a similar 33% incidence of grade IV/V non-hematologic toxicity, when given with PSC 833. Mitoxantrone/etoposide (M/E) doses were escalated in fixed ratio from a starting dose of M: 4 mg/M(2) and E: 40 mg/M(2), to M: 7 mg/M(2) and E: 70 mg/M(2), in successive cohorts of eight patients each. PSC 833 was well tolerated and the MTD of this M/E regimen with PSC 833 in this population was M: 6 mg/M(2) and E: 60 mg/M(2). The complete response (CR) rate for all patients was 50% (15/30) and was considerably higher for de novo than for secondary AML. These data suggest that the addition of PSC 833 to an M/E regimen for older patients with untreated AML is well tolerated but requires a reduction in M/E dosing to avoid increased toxicity.
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result sql = A phase I study of induction chemotherapy for older patients with newly diagnosed acute myeloid leukemia (AML) using mitoxantrone, etoposide, and the MDR modulator PSC 833: a southwest oncology group study 9617.
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char = d;code = 100
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char = i;code = 105
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char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = e;code = 101
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char = o;code = 111
char = m;code = 109
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char = l;code = 108
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char = e;code = 101
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char = o;code = 111
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char = );code = 41
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char = a;code = 97
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char = e;code = 101
char = ;code = 32
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char = r;code = 114
char = ;code = 32
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char = l;code = 108
char = l;code = 108
char = ;code = 32
char = p;code = 112
char = a;code = 97
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char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
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char = a;code = 97
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char = ;code = 32
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char = ;code = 32
char = (;code = 40
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char = n;code = 110
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char = w;code = 119
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char = ;code = 32
char = c;code = 99
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char = n;code = 110
char = s;code = 115
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = b;code = 98
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = v;code = 118
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
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char = o;code = 111
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char = L;code = 76
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
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char = s;code = 115
char = e;code = 101
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char = d;code = 100
char = a;code = 97
char = t;code = 116
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char = u;code = 117
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
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char = ;code = 32
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char = t;code = 116
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char = e;code = 101
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char = d;code = 100
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char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = P;code = 80
char = S;code = 83
char = C;code = 67
char = ;code = 32
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char = 3;code = 51
char = 3;code = 51
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char = t;code = 116
char = o;code = 111
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char = i;code = 105
char = t;code = 116
char = h;code = 104
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char = u;code = 117
char = i;code = 105
char = r;code = 114
char = e;code = 101
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char = ;code = 32
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char = e;code = 101
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = M;code = 77
char = /;code = 47
char = E;code = 69
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = v;code = 118
char = o;code = 111
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
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
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result sql = Older patients with acute myelogenous leukemia (AML) have overexpression of P-glycoprotein (Pgp+), and this has been shown to correlate quantitatively with therapeutic outcome. Since Pgp-mediated efflux of cytotoxic drugs can be inhibited by the cyclosporine analogue, PSC 833, we investigated the use of this agent with a 5-day mitoxantrone/etoposide regimen in patients over age 55 with newly diagnosed AML. Previous studies suggested a 33% incidence of grade IV/V non-hematologic toxicity with the use of mitoxantrone 10 mg/M(2) and etoposide 100 mg/M(2), each for 5 days, in this patient population. Since PSC 833 alters the pharmacokinetic excretion of MDR-related cytotoxins, this phase I dose-finding study was performed to identify doses of mitoxantrone/etoposide associated with a similar 33% incidence of grade IV/V non-hematologic toxicity, when given with PSC 833. Mitoxantrone/etoposide (M/E) doses were escalated in fixed ratio from a starting dose of M: 4 mg/M(2) and E: 40 mg/M(2), to M: 7 mg/M(2) and E: 70 mg/M(2), in successive cohorts of eight patients each. PSC 833 was well tolerated and the MTD of this M/E regimen with PSC 833 in this population was M: 6 mg/M(2) and E: 60 mg/M(2). The complete response (CR) rate for all patients was 50% (15/30) and was considerably higher for de novo than for secondary AML. These data suggest that the addition of PSC 833 to an M/E regimen for older patients with untreated AML is well tolerated but requires a reduction in M/E dosing to avoid increased toxicity.
Publication: Leuk. Res. 2000 Jul ;24(7)::567-74.
Publication Date: 2000 Jul
Study Author(s): Chauncey, T R;Rankin, C;Anderson, J E;Chen, I;Kopecky, K J;Godwin, J E;Kalaycio, M E;Moore, D F;Shurafa, M S;Petersdorf, S H;Kraut, E H;Leith, C P;Head, D R;Luthardt, F W;Willman, C L;Appelbaum, F R;
Institution: University of Washington School of Medicine, Seattle, WA, USA.
Shortcut link to this study:
Publication Date: 2000 Jul
Study Author(s): Chauncey, T R;Rankin, C;Anderson, J E;Chen, I;Kopecky, K J;Godwin, J E;Kalaycio, M E;Moore, D F;Shurafa, M S;Petersdorf, S H;Kraut, E H;Leith, C P;Head, D R;Luthardt, F W;Willman, C L;Appelbaum, F R;
Institution: University of Washington School of Medicine, Seattle, WA, USA.
Shortcut link to this study:
Older patients with acute myelogenous leukemia (AML) have overexpression of P-glycoprotein (Pgp+), and this has been shown to correlate quantitatively with therapeutic outcome. Since Pgp-mediated efflux of cytotoxic drugs can be inhibited by the cyclosporine analogue, PSC 833, we investigated the use of this agent with a 5-day mitoxantrone/etoposide regimen in patients over age 55 with newly diagnosed AML. Previous studies suggested a 33% incidence of grade IV/V non-hematologic toxicity with the use of mitoxantrone 10 mg/M(2) and etoposide 100 mg/M(2), each for 5 days, in this patient population. Since PSC 833 alters the pharmacokinetic excretion of MDR-related cytotoxins, this phase I dose-finding study was performed to identify doses of mitoxantrone/etoposide associated with a similar 33% incidence of grade IV/V non-hematologic toxicity, when given with PSC 833. Mitoxantrone/etoposide (M/E) doses were escalated in fixed ratio from a starting dose of M: 4 mg/M(2) and E: 40 mg/M(2), to M: 7 mg/M(2) and E: 70 mg/M(2), in successive cohorts of eight patients each. PSC 833 was well tolerated and the MTD of this M/E regimen with PSC 833 in this population was M: 6 mg/M(2) and E: 60 mg/M(2). The complete response (CR) rate for all patients was 50% (15/30) and was considerably higher for de novo than for secondary AML. These data suggest that the addition of PSC 833 to an M/E regimen for older patients with untreated AML is well tolerated but requires a reduction in M/E dosing to avoid increased toxicity.
PMID: 10867130
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