Practical management of NSCLC patients with long-term bevacizumab treatment: a report of four cases

GJM Herder,1 H Codrington,2 CD Colder,3 JG Aerts4,51St Antonius Hospital, Nieuwegein, The Netherlands; 2Haga Hospital, The Hague, The Netherlands; 3St Jansdal Hospital, Harderwijk, The Netherlands; 4Amphia Hospital, Breda; 5Erasmus MC Rotterdam, The NetherlandsIntroduction: Previous research showed that the addition of bevacizumab (a monoclonal antibody against vascular endothelial growth factor [VEGF]) to chemotherapy resulted in a significant efficacy benefit in the treatment of selected patients with advanced nonsquamous non–small cell lung cancer (NSCLC). However, the occurrence and management of adverse events (AEs) during long-term maintenance treatment with bevacizumab is not well known.Methods: This report presents a descriptive analysis, including the management of AEs, of four patients with advanced NSCLC, who received a relatively long period of bevacizumab maintenance treatment.Results: In patient 1, a 72-year-old retired man with stage cT2N2M1b NSCLC, the only AE related to bevacizumab was a grade 1 rhinorrhea. Treatment resulted in a stable disease, with duration of response of 38 months. Patient 2 had NSCLC stage cT4N3M1b and developed a cavitation and infection after the first cycle of chemotherapy and bevacizumab, which caused a temporary decrease of her quality of life. Bevacizumab therapy resulted in a partial response, with duration of response of 15 months. A 52-year-old female (patient 3) with stage T2bN2M1a NSCLC is currently under treatment and has so far received 42 cycles of maintenance bevacizumab, with stabilized response (duration of response of 29 months) and no noteworthy AEs. The last patient is a 74-year-old male farmer with NSCLC T1N0M1, whose response has lasted for more than 3 years, with until now, no AEs.Conclusion: Our retrospective findings of these four patients show the long-term efficacy and safety of bevacizumab treatment in a real-life setting.Keywords: lung cancer, non–small cell lung cancer, maintenance treatment, safety managemen

Glucose-dependent leukocyte activation in patients with type 2 diabetes mellitus, familial combined hyperlipidemia and healthy controls

Background. Leukocyte activation has been associated with vascular complications in type 2 diabetes mellitus (T2DM). Hyperglycemia may be involved in this leukocyte activation. Our aim was to investigate the role of elevated glucose concentrations on leukocyte activation in patients with a wide range of insulin sensitivity. Methods. Leukocyte activation was determined after ingestion of 75 gram glucose in subjects with T2DM, familial combined hyperlipidemia (FCH) and healthy controls. Leukocyte activation markers were measured by flow cytometry. Postprandial changes were calculated as the area under the curve (AUC), and the incremental area under the curve corrected for baseline values (dAUC). Results. 51 subjects (20 T2DM, 17 FCH and 14 controls) were included. Fasting neutrophil CD66b expression and CD66b-AUC were respectively 36% and 39% higher in T2DM patients than in controls (p = 0.004 and p = 0.003). Fasting neutrophil CD66b expression correlated positively with glucose-AUC (Spearman's rho 0.481, p < 0.001) and HbA1c (rho 0.433, p = 0.002). Although fasting monocyte CD11b expression was not significantly different between subjects, monocyte CD11b-AUC was 26% higher in T2DM than in controls (p = 0.006). Similar trends were observed for FCH patients. Monocyte CD11b-dAUC correlated positively with glucose-AUC (rho 0.322, p = 0.022) and HbA1c (rho 0.319, p = 0.023). Conclusions. These data suggest that both acute and chronic hyperglycemia, associated with insulin resistance as seen in T2DM and FCH, are involved in the increased fasting and postprandial leukocyte activation observed in these conditions. (C)) 2015 Elsevier Inc. All rights reserved

Traditional versus up-front [F-18] fluorodeoxyglucose-positron emission tomography staging of non-small-cell lung cancer: A Dutch cooperative randomized study

Purpose We investigated whether application of positron emission tomography (PET) immediately after first presentation might simplify staging while maintaining accuracy, as compared with traditional strategy in routine clinical setting. Methods At first presentation, patients with a provisional diagnosis of lung cancer without overt dissemination were randomly assigned to traditional work-up (TWU) according to international guidelines or early PET followed by histologic/cytologic verification of lesions, or imaging and follow-up. Patients with [F-18] fluorodeoxyglucose ((18)FDG) -avid, noncentral tumors without suspicion of mediastinal or distant metastases on PET proceeded directly to thoracotomy. Follow-up in presumed benign lesions was at least 12 months. In patients treated with surgery or neoadjuvant therapy, the quality of staging was measured by comparing the clinical stage to the final stage (combination of peroperative staging and 6 months of follow-up). To investigate test substitution, we analyzed the number of (non)invasive tests to achieve clinical TNM staging, and its associated costs. Results Between 1999 and 2001, 465 patients (233 TWU, 232 PET) were enrolled at 22 hospitals. The mean (standard deviation) number of procedures to finalize staging was equal in the TWU arm and the PET arm: 7.9 (2.0) v 7.9 (1.9), P = .90, respectively. Mediastinoscopies occurred significantly less often in the PET arm. Agreement between clinical and final stage was good in both arms (kappa = .85 v .78; P = .07). Costs did not differ significantly. Conclusion Up-front (18)FDG-PET in patients with (suspected) lung cancer does not reduce the overall number of diagnostic test, but it maintains quality of TNM staging with the use of less invasive surgery