Safety, Pharmacokinetics, and Pharmacodynamics of the Insulin-Like Growth Factor Type 1 Receptor Inhibitor Figitumumab (CP-751,871) in Combination with.

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Safety, Pharmacokinetics, and Pharmacodynamics of the Insulin-Like Growth Factor Type 1 Receptor Inhibitor Figitumumab (CP-751,871) in Combination with Paclitaxel and Carboplatin Daniel D. Karp, MD, Michael N. Pollak, MD, Roger B. Cohen, MD, Peter D. Eisenberg, MD, Paul Haluska, MD, PhD, Donghua Yin, PhD, Allan Lipton, MD, Laurence Demers, PhD, Kim Leitzel, MSc, Mary L. Hixon, PhD, Leon W. Terstappen, MD, PhD, Linda Garland, MD, Luis G. Paz-Ares, MD, PhD, Felipe Cardenal, MD, Corey J. Langer, MD, Antonio Gualberto, MD, PhD Journal of Thoracic Oncology Volume 4, Issue 11, Pages 1397-1403 (November 2009) DOI: 10.1097/JTO.0b013e3181ba2f1d Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Mean (±SD) plasma concentration-time profiles of figitumumab (F) after cycles 1 and 3 of treatment. Journal of Thoracic Oncology 2009 4, 1397-1403DOI: (10.1097/JTO.0b013e3181ba2f1d) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Time profiles of circulating endothelial cell (CEC) counts in (A) all patients with providing samples for CEC enumeration (N = 22) and (B) according to figitumumab (F) treatment doses ≤6 mg/kg (N = 12) or 10 to 20 mg/kg (N = 10). Data are represented as box plots (minimum, 25 percentile, median, 75 percentile, maximum) and individual CEC counts. Values outside the box plots are considered outliers (smaller or larger than the minimum or maximum estimates). Journal of Thoracic Oncology 2009 4, 1397-1403DOI: (10.1097/JTO.0b013e3181ba2f1d) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 Soluble insulin-like growth factor type 1 receptor (IGF-1R) extracellular domain (sIGF-1R), IGF binding protein-3 (IGFBP-3), and free IGF-1 (fIGF-1) levels by figitumumab (F) dose. Data are represented relative to baseline levels. Journal of Thoracic Oncology 2009 4, 1397-1403DOI: (10.1097/JTO.0b013e3181ba2f1d) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 4 Analysis of insulin-like growth factor (IGF) binding protein-3 (IGFBP-3), free IGF-1 (fIGF-1) levels, and fIGF-1/IGFBP-3 ratio in responders (R) and nonresponders (NR) to treatment, according to RECIST, at figitumumab (F) treatment doses ≤6 mg/kg (N = 18) or 10 to 20 mg/kg (N = 22). Journal of Thoracic Oncology 2009 4, 1397-1403DOI: (10.1097/JTO.0b013e3181ba2f1d) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions