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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.


Saif M.W.,Yale University | Syrigos K.,Oncology Unit GPP | Penney R.,Yale University | Kaley K.,Yale University
Anticancer Research | Year: 2010

Background: No therapeutic standard of care exists for patients who have progressed following first-line treatment with a gemcitabine-based regimen with advanced pancreatic cancer. Approximately half of the patients failing upfront treatment present with ECOG PS 1-2 and are willing to undergo further treatment. Docetaxel activity against pancreatic cancer is reported both in the preclinical and clinical setting. This study retrospectively evaluated the role of docetaxel as second-line therapy in patients with gemcitabine-refractory disease. Patients and Methods: Between January 2006 and November 2009, 17 patients (median age of 61 years) with advanced pancreatic adenocarcinoma, after receiving gemcitabine-containing chemotherapy as first-line median ECOG performance status 1 and with adequate organ function, were treated with either weekly docetaxel at 25 mg/m2 or 3-weekly docetaxel regimen (docetaxel at 75 mg/m2 or docetaxel-gemcitabine-capecitabine or docetaxel-gemcitabine) until progressive disease. Serum CA19-9 levels were measured every 3/4 weeks and CT scans performed after every eight/nine weeks. Results: Docetaxel dose intensity was 90% in the patients who received weekly docetaxel, 85% in docetaxel-erlotinib regimen and 65% in 3-weekly regimen (docetaxel-gemcitabine-capecitabine, docetaxel-gemcitabine). Only one objective response (6%) to treatment was obtained (docetaxel-gemcitabine), while 5 patients achieved stable disease (weekly docetaxel). Median progression-free survival was 8 weeks (range: 3-16 weeks) and median survival was 4.0 months (range: 2.0-6.5 months). No toxicity with grade >3 associated with docetaxel was observed. Conclusion: Docetaxel seems to have mild activity in the treatment of gemcitabine-resistant metastatic pancreatic cancer. Although some patients may benefit from the treatment, other dosing regimens and novel taxanes such as Nab-paclitaxel should be explored in this setting.


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

It is estimated that approximately 25% of all lung cancer cases are observed in never-smokers and its incidence is expected to increase due to smoking prevention programs. Risk factors for the development of lung cancer described include second-hand smoking, radon exposure, occupational exposure to carcinogens and to cooking oil fumes and indoor coal burning. Other factors reported are infections (HPV and Mycobacterium tuberculosis), hormonal and diatery factors and diabetes mellitus. Having an affected relative also increases the risk for lung cancer while recent studies have identified several single nucleotide polymorphisms associated with increased risk for lung cancer development in never smokers. Distinct clinical, pathology and molecular characteristics are observed in lung cancer in never smokers; more frequently is observed in females and adenocarcinoma is the predominant histology while it has a different pattern of molecular alterations. The purpose of this review is to summarize our current knowledge of this disease. © 2013 Elsevier Ireland Ltd.


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.


PubMed | Oncology Unit GPP
Type: Journal Article | Journal: Critical reviews in oncology/hematology | Year: 2013

It is estimated that approximately 25% of all lung cancer cases are observed in never-smokers and its incidence is expected to increase due to smoking prevention programs. Risk factors for the development of lung cancer described include second-hand smoking, radon exposure, occupational exposure to carcinogens and to cooking oil fumes and indoor coal burning. Other factors reported are infections (HPV and Mycobacterium tuberculosis), hormonal and diatery factors and diabetes mellitus. Having an affected relative also increases the risk for lung cancer while recent studies have identified several single nucleotide polymorphisms associated with increased risk for lung cancer development in never smokers. Distinct clinical, pathology and molecular characteristics are observed in lung cancer in never smokers; more frequently is observed in females and adenocarcinoma is the predominant histology while it has a different pattern of molecular alterations. The purpose of this review is to summarize our current knowledge of this disease.

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