Phase II Trials of Imatinib Mesylate and Docetaxel in Patients with Metastatic Non-small Cell Lung Cancer and Head and Neck Squamous Cell Carcinoma Anne.

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Phase II Trials of Imatinib Mesylate and Docetaxel in Patients with Metastatic Non-small Cell Lung Cancer and Head and Neck Squamous Cell Carcinoma Anne S. Tsao, MD, Suyu Liu, MS, Junya Fujimoto, PhD, Ignacio I. Wistuba, MD, J. Jack Lee, PhD, Edith M. Marom, MD, Chusilp Charnsangavej, MD, Frank V. Fossella, MD, BA, Hai T. Tran, PharmD, George R. Blumenschein, MD, Vassiliki Papadimitrakopoulou, MD, Merrill S. Kies, MD, Waun K. Hong, MD, David J. Stewart, MD Journal of Thoracic Oncology Volume 6, Issue 12, Pages 2104-2111 (December 2011) DOI: 10.1097/JTO.0b013e31822e7256 Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1. Survival curves for biomarker analyses from protocol 2004-0726. A–C, Immunohistochemical (IHC) expression levels of tumor tissue biomarkers by progression-free survival (PFS). A, A significant improvement in PFS when comparing any baseline IHC expression of platelet-derived growth factor receptor (PDGFR)α in the stroma to no IHC expression (p = 0.04) and in (B), any baseline IHC expression of PDGFRβ in the tumor cell cytoplasm to no IHC expression (p = 0.03). C, Comparison of low IHC expression of PDGFRβ in the stroma (≤10 score) with high IHC expression (>10) by PFS (p = 0.03). D, The overall survival results by any or no IHC expression of PDGFRα in the stromal tissue. Journal of Thoracic Oncology 2011 6, 2104-2111DOI: (10.1097/JTO.0b013e31822e7256) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2. Perfusion computed tomography (CT) scan results on a 63-year-old man with metastatic non-small cell lung cancer (NSCLC). Baseline contrast-enhanced chest CT (A) at the level of the pulmonary trunk (P) demonstrates a 3.5 cm primary right upper lobe lung cancer (arrowhead). One month later, after one cycle of imatinib mesylate-docetaxel was administered, a contrast-enhanced chest CT shows no significant anatomic change in size, but central tumor cavitation was observed (B, arrow). Baseline CT blood flow (C) was 72.3 ml/min/g and increased 10% on the postcycle 1 perfusion CT scan (D) to 80.4 ml/min/g. Blood volume at baseline (E) was 2.6 ml/g and decreased 7% to 2.4 ml/g on the postcycle 1 perfusion CT scan (F). This patient had toxicity with the regimen and was removed from the study after cycle 2 of treatment. By RECIST, the patient had stable disease after two cycles of therapy for imatinib mesylate-docetaxel. Journal of Thoracic Oncology 2011 6, 2104-2111DOI: (10.1097/JTO.0b013e31822e7256) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3. Perfusion computed tomography (CT) scan results on a 43-year-old woman with metastatic non-small cell lung cancer (NSCLC). Baseline contrast-enhanced chest CT (A) demonstrates the primary lung cancer (arrow). After 1 cycle of imatinib mesylate-docetaxel was administered, a contrast-enhanced chest CT (B) shows no significant change in anatomic size. Baseline CT blood flow (C) was 13.5 ml/min/g, which decreased 9% on the postcycle 1 perfusion CT scan (D) to 12.3 ml/min/g. Blood volume at baseline (E) was 3.2 ml/g and decreased 16% to 2.7 ml/g on the postcycle 1 perfusion CT scan (F). This patient developed a minor response after cycle 2 of therapy but developed pneumonia during that time and was unable to continue on the imatinib mesylate for cycle 3 of therapy and was removed from the study. Journal of Thoracic Oncology 2011 6, 2104-2111DOI: (10.1097/JTO.0b013e31822e7256) Copyright © 2011 International Association for the Study of Lung Cancer Terms and Conditions