Pooled Analysis of Elderly Patients with Non-small Cell Lung Cancer Treated with Front Line Docetaxel/Gemcitabine Regimen: The Hellenic Oncology Research Group Experience

IntroductionThirty to 40% of patients with non-small cell lung cancer (NSCLC) are older than 70 years and rarely are enrolled in clinical trials. Moreover, in clinical practice, >75% of patients older than 65 years with metastatic NSCLC never receive any kind of chemotherapy.PurposeTo retrospectively evaluate the impact of age on efficacy and toxicity of chemotherapy regimens in patients with advanced NSCLC treated with the docetaxel-gemcitabine combination.Patients and MethodsPooled data from six clinical trials of the Hellenic Oncology Research Group were analyzed. According to their age, patients were divided into two groups: those with age <70 years and those with ≥70 years.ResultsA total of 858 patients were included in this analysis. Six hundred sixty-six (77.6%) patients were younger than 70 years, whereas 192 (22.4%) patients where ≥70-year-old. Overall response rate was 30.3% and 30.2% for patients <70 years and ≥70 years, respectively (p = 0.974). The median time to tumor progression was 4.1 and 4.5 months for patients <70 years and ≥70 years, respectively (p = 0.948). Median overall survival was 9.9 and 9.2 months for patients <70 and ≥70, respectively (p = 0.117). The multivariate analysis revealed performance status (PS) (p = 0.0001) and stage (p = 0.0001) as independent factors with significant impact on the hazard of death. Chemotherapy was well tolerated, but the incidence of grade III/IV mucositis was significantly higher in elderly patients (0.2% versus 1.5% for patients <70 versus ≥70 years, respectively; p = 0.011).ConclusionThe docetaxel/gemcitabine regimen has a comparable efficacy and tolerance in young (<70 years) and elderly (≥70 years) patients

A randomized phase III study of the docetaxel/carboplatin combination versus docetaxel single-agent as second line treatment for patients with advanced/metastatic Non-Small Cell Lung Cancer

<p>Abstract</p> <p>Background</p> <p>To compare the activity and toxicity of docetaxel/carboplatin (DC) doublet vs single agent docetaxel (D) as second-line treatment in patients with advanced non-small cell lung cancer (NSCLC).</p> <p>Methods</p> <p>Patients pre-treated with front-line platinum-free regimens, were randomized to receive either docetaxel/carboplatin (DC), (docetaxel 50 mg/m²; carboplatin AUC4; both drugs administered on days 1 and 15) or docetaxel single-agent (D), (docetaxel 50 mg/m²on days 1 and 15).</p> <p>Results</p> <p>Response rate was similar between the two arms (DC vs D: 10.4% vs 7.7%; p = 0.764). After a median follow-up time of 28.0 months for DC arm and 34.5 months for D arm, progression free survival (PFS) was significantly higher in the DC arm (DC vs D:3.33 months vs 2.60 months; p-value = 0.012), while no significant difference was observed in terms of overall survival (OS) (DC vs D: 10.3 months vs 7.70 months; p-value = 0.550). Chemotherapy was well-tolerated and grade III/IV toxicities were relatively infrequent. No toxic deaths were observed.</p> <p>Conclusions</p> <p>This study has not achieved its primary objective of significant OS prolongation with docetaxel/carboplatin combination over single-agent docetaxel in patients who had not received front-line docetaxel; however, the docetaxel/carboplatin combination was associated with a significant clinical benefit in terms of PFS.</p

Lung metastasis and pancreatic carcinoma

Case Repor

Targeting the Interplay between HDACs and DNA Damage Repair for Myeloma Therapy

Multiple myeloma (MM) is a malignancy of terminally differentiated plasma cells, and accounts for 10% of all hematologic malignancies and 1% of all cancers. MM is characterized by genomic instability which results from DNA damage with certain genomic rearrangements being prognostic factors for the disease and patients’ clinical response. Following genotoxic stress, the evolutionary conserved DNA damage response (DDR) is activated and, in turn, coordinates DNA repair with cell-cycle events. However, the process of carcinogenesis cannot be attributed only to the genetic alterations, but also involves epigenetic processes. Regulation of expression and activity of key players in DNA repair and checkpoint proteins are essential and mediated partly by posttranslational modifications (PTM), such as acetylation. Crosstalk between different PTMs is important for regulation of DNA repair pathways. Acetylation, which is mediated by acetyltransferases (HAT) and histone deacetylases (HDAC), not only affects gene expression through its modulation of histone tails but also has recently been implicated in regulating non-histone proteins. Currently, several HDAC inhibitors (HDACi) have been developed both in pre-clinical and clinical studies, with some of them exhibiting significant anti-MM activities. Due to reversibility of epigenetic changes during the evolutionary process of myeloma genesis, the potency of epigenetic therapies seems to be of great importance. The aim of the present paper is the summary of all data on the role of HDACi in DDR, the interference with each DNA repair mechanism and the therapeutic implications of HDACi in MM

Cancer therapy and cardiovascular risk: focus on bevacizumab

Recognition and management of treatment-related cardiovascular toxicity, defined as either an acute cardiac event or a chronic condition, has been tightly integrated into routine cancer care and has become an important component in treatment selection. Several chemotherapeutic agents, such as anthracyclines, are traditionally characterized as cardiotoxic, but cardiovascular adverse events are also associated with commonly used molecular targeted therapies. In the past decade, bevacizumab, a monoclonal humanized antibody against vascular endothelial growth factor, has been introduced in the treatment of a variety of metastatic malignancies. Despite its efficacy, bevacizumab has been associated with significant risk of cardiovascular complications, such as hypertension, cardiac ischemia, and congestive heart failure. This review will focus on the cardiovascular toxicity of bevacizumab, providing the latest evidence on the incidence, clinical spectrum, risk factors, and responsible mechanisms

Extensive cutaneous metastases of pancreatic adenocarcinoma: a case report and review of the literature

Herein, we present the case of a patient with pancreatic cancer and nonumbilical cutaneous metastasis. Patients with pancreatic adenocarcinomas can develop extensive cutaneous metastases involving not only abdominal skin but also other unusual sites such as the scrotum

Do elderly patients with non-small cell lung cancer get the best out of recent advances in first-line treatment? A comparative study in two tertiary cancer centers in Greece

Background: Elderly patients with advanced non-small cell lung cancer (NSCLC) are thought to receive suboptimal treatment mainly due to concerns for poor compliance and/or excessive toxicity. Patients and Methods: Using the age of 70 years as the pre-defined cut-off, we compared elderly patients with advanced NSCLC suitable for first line chemotherapy with their younger counterparts in terms of: i) diagnosis and disease characteristics ii) adherence to treatment schedule, including dose intensity (DI), and relative dose intensity (RDI), iii) toxicity, tolerance, and efficacy outcomes. Results: Among 292 eligible patients, data were available for 245, of whom 107 (43.7%) belonged to the elderly group. This group was more likely to present with co-morbidities, non-smoking current status and diagnosis based on cytology alone. As compared to the non-elderly, elderly patients were more likely to receive single-agent therapy (8.0% vs. 29.2% respectively, p &lt; 0.001) and less likely to receive platinum-based chemotherapy (80.3% vs. 57.9%, p &lt; 0.001). Elderly patients also received docetaxel (24.3% vs. 40.4%), and bevacizumab (7.5% vs. 21.3%) significantly less often and received oral vinorelbine (24.3% vs. 11.8%) more frequently. Non-elderly patients were more likely to receive any of the cytotoxic drugs with RDI &gt; 0.8 (49.6% vs. 33.0%, p = 0.012) and RDI &gt; 0.9 (29.6% vs. 16%, p = 0.015). Substantial toxicity, as well as median overall survival did not differ significantly between the two groups. Conclusions: Only one third of the elderly patients received at least 80% of the scheduled treatment intensity. Nearly half received diagnosis based on cytology alone, which may deprive them from new, histology-driven, therapeutic approaches. (C) 2014 Elsevier Ltd. All rights reserved

In vitro postantibiotic effect of colistin on multidrug-resistant Acinetobacter baumannii

Infections by multi drug-resistant Acinetobacter baumannii constitute an increasing threat for critically ill patients. Colistin is often the only antimicrobial retaining activity against these strains. The postantibiotic effect (PAE) of colistin was studied on 19 isolates of A. baumannii resistant to ampicillin/sulbactam, ciprofloxacin, and carbapenems with the viable count method. The mean PAEs of I X MIC and 4 x MIC concentrations of colistin on the tested isolates were 3.90 and 4.48 h, respectively, indicating that a modified dosage scheme with increased dosing intervals might retain activity whereas minimizing the incidence of adverse effects. (c) 2007 Elsevier Inc. All rights reserved