TY - JOUR
T1 - Phase I dose escalation study of the anti-insulin-like growth factor-I receptor monoclonal antibody CP-751,871in patients with refractory solid tumors
AU - Haluska, Paul
AU - Shaw, Heather M.
AU - Batzel, Gretchen N.
AU - Yin, Donghua
AU - Molina, Julian R.
AU - Molife, L. Rhoda
AU - Yap, Timothy A.
AU - Roberts, M. Luisa
AU - Sharma, Amarnath
AU - Gualberto, Antonio
AU - Adjei, Alex A.
AU - De Bono, Johann S.
PY - 2007/10/1
Y1 - 2007/10/1
N2 - Purpose: This phase I study was undertaken to define the maximum tolerated dose, safety, and pharmacokinetic profile of CP-751,871. Experimental Design: Using a rapid dose escalation design, patientswith advanced nonhematologic malignancies were treated with CP-751,871 in four dose escalation cohorts. CP-751,871 was administered i.v. on day 1 of each 21-day cycle. Pharmacokinetic evaluation was done in all treatment cohorts during cycles1 and 4. Results: Twenty-four patients received 110 cycles at four dose levels. The maximum tolerated dose exceeded the maximal feasible dose of 20 mg/kg and, thus, was not identified. Treatment-related toxicities were generally mild. The most common adverse events were hyperglycemia, anorexia, nausea, elevated aspartate aminotransferase, elevated γ-glutamyltransferase, diarrhea, hyperuracemia, and fatigue. At 20 mg/kg, 10 of 15 patients experienced stability of disease. Two of these patients experienced long-term stability. There were no objective responses. Pharmacokinetic analysis revealed a dose-dependent increase in CP-751,871 exposure and ∼2-fold accumulation on repeated dosing in 21-day cycles. Plasma concentrations of CP-751,871 attained were several log-fold greater than the biologically active concentration. Treatment with CP-751,871 increased serum insulin and human growth hormone levels, with modest increases in serum glucose levels. Conclusions: CP-751,871 has a favorable safety profile and was well tolerated when given in continuous cycles. At themaximal feasible dose of 20 mg/kg, there was amoderate accumulation in plasma exposure, and most of the treated patients experienced stability of disease.
AB - Purpose: This phase I study was undertaken to define the maximum tolerated dose, safety, and pharmacokinetic profile of CP-751,871. Experimental Design: Using a rapid dose escalation design, patientswith advanced nonhematologic malignancies were treated with CP-751,871 in four dose escalation cohorts. CP-751,871 was administered i.v. on day 1 of each 21-day cycle. Pharmacokinetic evaluation was done in all treatment cohorts during cycles1 and 4. Results: Twenty-four patients received 110 cycles at four dose levels. The maximum tolerated dose exceeded the maximal feasible dose of 20 mg/kg and, thus, was not identified. Treatment-related toxicities were generally mild. The most common adverse events were hyperglycemia, anorexia, nausea, elevated aspartate aminotransferase, elevated γ-glutamyltransferase, diarrhea, hyperuracemia, and fatigue. At 20 mg/kg, 10 of 15 patients experienced stability of disease. Two of these patients experienced long-term stability. There were no objective responses. Pharmacokinetic analysis revealed a dose-dependent increase in CP-751,871 exposure and ∼2-fold accumulation on repeated dosing in 21-day cycles. Plasma concentrations of CP-751,871 attained were several log-fold greater than the biologically active concentration. Treatment with CP-751,871 increased serum insulin and human growth hormone levels, with modest increases in serum glucose levels. Conclusions: CP-751,871 has a favorable safety profile and was well tolerated when given in continuous cycles. At themaximal feasible dose of 20 mg/kg, there was amoderate accumulation in plasma exposure, and most of the treated patients experienced stability of disease.
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U2 - 10.1158/1078-0432.CCR-07-1118
DO - 10.1158/1078-0432.CCR-07-1118
M3 - Article
C2 - 17908976
AN - SCOPUS:35348815620
SN - 1078-0432
VL - 13
SP - 5834
EP - 5840
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 19
ER -