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Ymittos Athens, Greece

Wasif Saif M.,Yale University | Syrigos K.,Oncology Unit GPP | Kaley K.,Yale University | Isufi I.,Yale University
Anticancer Research | Year: 2010

Background: Oxaliplatin use in gastrointestinal malignancies is limited by neurotoxicity. This study aimed to assess the efficacy of pregabalin (LYRICA®) in the treatment of oxaliplatin-induced neurotoxicity. Patients and Methods: A total of 23 gastrointestinal cancer patients with grade 2 and 3 oxaliplatin-induced sensory neuropathy were treated with pregabalin up to a target dose of 150mg orally (PO) three times a day (tid) based on benefit and tolerance. Neurological symptoms were serially evaluated. Results: The target dose of 150 mg tid provided the best benefit, but patients benefited even at lower doses. Onset of benefit was observed in 2-6 weeks. In the majority of patients (48%), neuropathy improved by 1 to 2 grades. Conclusion: Pregabalin significantly reduced the severity of oxaliplatin-induced sensory neuropathy. Being more potent than gabapentin, pregabalin achieved efficacy at lower doses and should lead to fewer dose-related side effects, although this remains to be established in a head-to-head trial.

Pallis A.G.,University of Crete | Syrigos K.N.,Oncology Unit GPP
Lung Cancer | Year: 2013

Improvements in our understanding of the molecular biology of cancer have shifted management of lung cancer toward molecular-guided, individualized treatment. Development of epidermal growth factor receptor tyrosine kinase inhibitors, erlotinib and gefitinib, represent the best example of this approach. Erlotinib was tested as second/third line treatment in unselected population of patients and demonstrated a statistically significant prolongation of overall survival, while gefitinib was shown to be non-inferior to docetaxel as second line treatment. The discovery of EGFR activating mutations facilitated the selection of patients most likely to benefit from erlotinib/gefitinib. These drugs in patients with EGFR activating mutations offer an increased progression free survival and significantly higher response rates compared to chemotherapy. The purpose of this paper is to present the relevant clinical data, describe the predictive markers available for TKIs treatment in NSCLC, and describe the mechanisms associated with resistance to treatment with these agents. © 2013 Elsevier Ireland Ltd.

Maintenance treatment has been intensively investigated in the field of advanced/metastatic non-small lung cancer in order to improve outcomes in this devastating disease. Two different approaches have been evaluated; the so-called continuation maintenance when the maintenance agent was part of initial therapy and is continued in the absence of disease progression ("maintained") or switch maintenance when a third agent is initiated after a defined number of cycles chemotherapy in the absence of disease progression. Several phase III trials with both chemotherapeutic and targeted agents have demonstrated either PFS prolongation (continuation maintenance) or both PFS and OS benefit (switch maintenance). Currently, erlotinib and pemetrexed are registered as maintenance treatment in patients with NSCLC not progressing after four cycles of standard platinum-based doublet chemotherapy. However, the development of maintenance treatment has raised a series of questions such as the role of treatment-free intervals, the timing of second-line treatment, selection of patients for maintenance treatment and selection of the most proper agent, and trial design issues such as optimal end-points. The purpose of this paper is to present and discuss the current trials investigating the main treatment paradigms and argue on the above mentioned questions. © 2012.

Pallis A.G.,University of Crete | Syrigos K.N.,Oncology Unit GPP
Critical Reviews in Oncology/Hematology | Year: 2013

Recent insight into the molecular biology of cancer and mechanisms of tumorigenesis, has allowed for the identification of several potential molecular targets and the development of novel " targeted therapies". One of the most active research fields in NSCLC is the discovery of therapies that target angiogenesis. The vascular endothelial growth factor (VEGF) pathway represents a crucial component of the tumor angiogenesis process. Two different strategies have been developed in clinical practice in order to restrict tumor vasculature development; either the use of monoclonal antibodies against VEGF or small molecule tyrosine kinase inhibitors to target the tyrosine kinase domain of VEGF receptor. Among these agents that have been tested bevacizumab, a monoclonal antibody against VEGF, has been approved for the treatment of metastatic NSCLC in combination with chemotherapy, while several other agents are under phase III investigation. Moreover, several issues such as predictive biomarkers of response to antiangiogenic therapy and mechanisms of resistance to these agents remain to be elucidated. The purpose of this paper is to present the current status of antiangiogenic therapies in the treatment of NSCLC and to discuss these issues. © 2012 Elsevier Ireland Ltd.

Koutsokera A.,Amalia Fleming General Hospital | Kiagia M.,Oncology Unit GPP | Saif M.W.,Tufts University | Souliotis K.,Oncology Unit GPP | Syrigos K.N.,Oncology Unit GPP
Clinical Lung Cancer | Year: 2013

Lung cancer is the leading cause of cancer death worldwide. Because of high incidence rates and low survival rates, it is important to study the risk factors that may help prevent the disease from developing. It has been well established that cigarette smoking is the most important risk factor for lung cancer. Nonetheless it is likely that there are other modifiable risk factors that would assist in the prevention of lung cancer. Research on factors such as nutrition and physical activity and their influence on lung cancer has been carried out for nearly 3 decades. A systematic review in the MEDLINE database of published studies was conducted, focusing on systematic reviews, meta-analyses, and large prospective studies. The association between physical activity and lung cancer has been conflicting. Among the researched studies, 10 showed an inverse association, whereas 11 reported no association. A meta-analysis that was conducted from 1996 to October 2003 showed that leisure physical activity (LPA) prevents lung cancer. Data from 11 cohort and case-control studies showed an inverse relationship between fruit and vegetable consumption and lung cancer. Evidence from case-control studies suggests a positive association between meat intake and risk of lung cancer, although several more recent studies have presented doubts about these findings. The possible association of physical activity, nutrition, and the risk of lung cancer development remains controversial. Further prospective studies should be conducted to determine the potential influence of these 2 risk factors. © 2013 Elsevier Inc.

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