Tian-Qing Chu1, Hao Ding2, David H Garfield3, Ai-Qin Gu1, Jun Pei1, Wei-Dong Du4, Bao-Hui Han5. 1. Department of Pulmonology, Shanghai Chest Hospital, Jiaotong University, Shanghai, China. 2. Department of Radiation Oncology, Eye, Ear, Nose & Throat Hospital, Fudan University, Shanghai, China. 3. Medical Department, Pro-Med Cancer Centers, Shanghai, China. 4. Division of Surgical Oncology and Thoracic Surgery, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.. Electronic address: weidongdu@hotmail.com. 5. Department of Pulmonology, Shanghai Chest Hospital, Jiaotong University, Shanghai, China. Electronic address: hbhxkyy@gmail.com.
Abstract
INTRODUCTION: Early prediction of the efficacy of a combination of an antiangiogenic drug with cytotoxic chemotherapy is a significant challenge. In that regard, circulating endothelial cells (CECs) and cytokeratins (CKs) seem to reflect their roles in both tumor angiogenesis and tumor cell death. METHODS:Patients with advanced, previously untreated non-small-cell lung cancer were randomly assigned to an endostatin treatment group (paclitaxel + carboplatin + endostatin) and a control group (paclitaxel + carboplatin + placebo). A total of 122 patients were evaluated, of whom 107 had measurements of blood CECs, CK8, caspase-cleaved CK18 (ccCK18), and uncleaved CK18 (CK18) before and at weeks 3 and 6 of treatment, respectively. RESULTS: Higher baseline CECs in patients with a tumor response (partial remission + stable disease, p = 0.002 for the entire group; p = 0.000 for the treatment group) were observed. The number of CECs decreased significantly after endostatin treatment (p = 0.000), whereas CK levels increased. Increased levels of ccCK18 and CK18, but not CK8, reached significance (p = 0.001 and p = 0.048, respectively) when compared with the baseline. Tumor response showed a strong correlation with reduction of CECs (p = 0.000) and increase of ccCK18 (p = 0.040) after endostatin therapy. Cutoff values of changes of CECs and ccCK18 for prediction of survival were 0.58/μl and 19.6 ng/ml, respectively. Reduction of CECs and increase of ccCK18 significantly correlated with longer median survival (p = 0.013 and p = 0.016 for progression-free survival; p = 0.009 and p = 0.012 for overall survival, respectively). CONCLUSIONS:CECs and CKs could be biomarkers for selecting patients with non-small-cell lung cancer who will benefit from treatment with endostatin in combination with paclitaxel plus carboplatin.
RCT Entities:
INTRODUCTION: Early prediction of the efficacy of a combination of an antiangiogenic drug with cytotoxic chemotherapy is a significant challenge. In that regard, circulating endothelial cells (CECs) and cytokeratins (CKs) seem to reflect their roles in both tumor angiogenesis and tumor cell death. METHODS:Patients with advanced, previously untreated non-small-cell lung cancer were randomly assigned to an endostatin treatment group (paclitaxel + carboplatin + endostatin) and a control group (paclitaxel + carboplatin + placebo). A total of 122 patients were evaluated, of whom 107 had measurements of blood CECs, CK8, caspase-cleaved CK18 (ccCK18), and uncleaved CK18 (CK18) before and at weeks 3 and 6 of treatment, respectively. RESULTS: Higher baseline CECs in patients with a tumor response (partial remission + stable disease, p = 0.002 for the entire group; p = 0.000 for the treatment group) were observed. The number of CECs decreased significantly after endostatin treatment (p = 0.000), whereas CK levels increased. Increased levels of ccCK18 and CK18, but not CK8, reached significance (p = 0.001 and p = 0.048, respectively) when compared with the baseline. Tumor response showed a strong correlation with reduction of CECs (p = 0.000) and increase of ccCK18 (p = 0.040) after endostatin therapy. Cutoff values of changes of CECs and ccCK18 for prediction of survival were 0.58/μl and 19.6 ng/ml, respectively. Reduction of CECs and increase of ccCK18 significantly correlated with longer median survival (p = 0.013 and p = 0.016 for progression-free survival; p = 0.009 and p = 0.012 for overall survival, respectively). CONCLUSIONS: CECs and CKs could be biomarkers for selecting patients with non-small-cell lung cancer who will benefit from treatment with endostatin in combination with paclitaxel plus carboplatin.
Authors: M Ilie; E Long; V Hofman; E Selva; C Bonnetaud; J Boyer; N Vénissac; C Sanfiorenzo; B Ferrua; C-H Marquette; J Mouroux; P Hofman Journal: Br J Cancer Date: 2014-01-28 Impact factor: 7.640
Authors: Elizabeth R Kessler; Lih-Jen Su; Dexiang Gao; Kathleen C Torkko; Michael Wacker; Mary Anduha; Nicole Chronister; Paul Maroni; E David Crawford; Thomas W Flaig; L Michael Glode; Elaine T Lam Journal: Integr Cancer Ther Date: 2018-10-05 Impact factor: 3.279