Papers by Alexios S Strimpakos
Annals of Oncology, 2009
Background: Carcinoembryonic antigen (CEA) flare may have a favourable response to chemotherapy, ... more Background: Carcinoembryonic antigen (CEA) flare may have a favourable response to chemotherapy, but its impact on survival is unknown. This study aimed to evaluate the incidence of CEA flare and its impact on objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Patients and methods: Patients with histologically proven advanced colorectal cancer undergoing first-line chemotherapy with three or more serial CEA measurements (one at baseline and two or more during treatment) were included. Patients were grouped according to CEA kinetic as flare (F), decreasing CEA, normal baseline CEA, stable CEA and increasing CEA (I).
Appropriate identification and validation of biomarkers as well as pharmacogenetics are important... more Appropriate identification and validation of biomarkers as well as pharmacogenetics are important in formulating patient-oriented, individualized chemotherapy or biological therapy in cancer patients. These markers can be especially valuable in pancreatic cancer, where high mortality and complex disease biology are frequently encountered. Recently, several advances have been made to further our knowledge in this specific area of pancreatic cancer. In the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting, researchers have presented several interesting results in biomarkers development: the identifications of 9 single nucleotide polymorphisms (SNPs) that is associated with positive efficacy of gemcitabine (Abstract #4022); the introduction of circulating tumor cells as a prognostic markers in pancreatic adenocarcinoma (Abstract #e14657); the re-affirmation of plasma cytidine deaminase (CDA) as a positive predictive markers for gemcitabine efficacy, as well as the postul...
The current achievements in pancreatic cancer diagnosis and treatment are disappointing for patie... more The current achievements in pancreatic cancer diagnosis and treatment are disappointing for patients and clinicians alike. Still, in the dawn of 2012, most patients are diagnosed at a late stage where cure is not feasible, with the majority going to succumb within the same year of diagnosis. Thus, the only hope for early and diagnosis and radical treatment is the invention of diagnostic and prognostic tests which might predict accurately patients who may develop this disease and those who have the most aggressive potential, so clinician adopt the appropriate strategy. In this paper we summarize the findings from the three most interesting research abstract as presented at the 2012 American Society of Clinical Oncology Gastrointestinal Cancers Symposium. In particular, we focus on Abstract #160 which shows the diagnostic utility of microRNA serum profiling in pancreatic cancer patients, on Abstract #201 which suggests a potential prognostic role of transforming growth factor (TGF)-be...
European Respiratory Journal, 2013
Background:Besides chemotherapy, E is an option in NSCLC pts especially in those with EGFR mutati... more Background:Besides chemotherapy, E is an option in NSCLC pts especially in those with EGFR mutations. Elderly pts enrolled in trials are fit without cM but in clinical practice most suffer from cM. Methods: Medical records of 1221 pts diagnosed with NSCLC between 2008-2012 were screened. We examined pts of 75 yrs for demographics, clinical data and Tx details. Results: 233/1221 NSCLC pts received E at any line. 53/233 (23%) were 75 yrs old. Male:female ratio was 34:19, median age 79 yrs (range 75-88). NSCLC subtypes included 31 adenoca, 8 squamous, 9 NOS and 5 others. 50/53 pts had cM (≥2 in 46 pts, 1 in 4pt). Main cM were cardiovascular disease (n=41), COPD (n=14), other cancer (n=10) and diabetes (n=8). 8 pts were tested for EGFR mutations (5 -ve, 3 +ve). Performance Status was satisfactory (ECOG 0-1) in 8 pts and poor (2-3) in 45pts. 8pts were treated with E 100mg and 45 pts with E 150mg (12 pts needed dose reduction). Complete follow up data were found in 46pts. Mean duration of...
Journal of the Pancreas, 2011
Neuroendocrine tumors of pancreas (PNET) are very rare, consisting of heterogeneous histological ... more Neuroendocrine tumors of pancreas (PNET) are very rare, consisting of heterogeneous histological subtypes with a variable natural history and different clinical manifestations. Although the vast majority of these neoplasms are sporadic, it is possible to be part of a genetic syndrome such as multiple endocrine neoplasia 1 (MEN-1) or tuberous sclerosis (TSC). When systemic treatment is required the options are limited and management strategy is generally based on experts’ consensus or clinical experience. The prognosis is usually better than in pancreatic adenocarcinoma, though poorly differentiated PNET behave aggressively and survival is shortened. Since last year, there has been a significant advance in the management of PNET, after reported data confirmed the efficacy of everolimus, an mTOR inhibitor, in patients with advanced disease. At the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Symposium, updated results of the phase III trial (RADIANT-3) regarding ...
Journal of the Pancreas, 2011
Appropriate identification and validation of biomarkers as well as pharmacogenetics are important... more Appropriate identification and validation of biomarkers as well as pharmacogenetics are important in formulating patient-oriented, individualized chemotherapy or biological therapy in cancer patients. These markers can be especially valuable in pancreatic cancer, where high mortality and complex disease biology are frequently encountered. Recently, several advances have been made to further our knowledge in this specific area of pancreatic cancer. In the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting, researchers have presented several interesting results in biomarkers development: the identifications of 9 single nucleotide polymorphisms (SNPs) that is associated with positive efficacy of gemcitabine (Abstract #4022); the introduction of circulating tumor cells as a prognostic markers in pancreatic adenocarcinoma (Abstract #e14657); the re-affirmation of plasma cytidine deaminase (CDA) as a positive predictive markers for gemcitabine efficacy, as well as the postul...
JOP : Journal of the pancreas, 2011
Despite the extensive research, mounting knowledge in the cancer field and enormous investments, ... more Despite the extensive research, mounting knowledge in the cancer field and enormous investments, pancreatic cancer remains a rather incurable disease with aggressive natural course and high mortality rate. The very slow progress is a result of the complex pathogenesis of this disease, which prevents us from targeting the culprit and making a step forward. Therefore, the field is still unexplored and this is a real challenge and opportunity for new ideas and novel approaches. In this paper, we will present the most interesting studies in the first line pancreatic cancer setting, presented at the American Society of Clinical Oncology (ASCO) 2011 Annual Meeting. While there are few studies testing the role of combining the cytotoxic S-1 and gemcitabine, the majority of the studies are examining the safety and impact of adding to the classic gemcitabine treatment novel molecular agents which target key pathways or overexpressed proteins.
Journal of the Pancreas, Mar 10, 2012
The standard current treatment options in advanced pancreatic cancer have demonstrated minimal or... more The standard current treatment options in advanced pancreatic cancer have demonstrated minimal or modest only efficacy for the majority of patients. Unfortunately, the mortality and morbidity remain high crying out for better treatments and results. With the exception of erlotinib, which received approval by the Food and Drug Administration of the United States in 2005, no other novel agents have since been added in our treatment quiver. Therefore, the search for novel approaches continuous at the laboratory and clinical level. At the 2012 American Society of Clinical Oncology Gastrointestinal Symposium, results of some interesting early phases clinical studies were presented. First, in Abstract #198, toxicity and efficacy results from the phase I/II study of cixutumumab, an insulin growth factor-1 receptor (IGF-1R) antibody combined with the standard gemcitabine and erlotinib treatment were presented, but the outcomes suggest no real clinical benefit. Second, the early safety and clinical data from the novel monoclonal antibody (ensituximab) against the mucin epitope NPC-1C in pancreatic and colon cancer patients were presented (Abstract #233) and again no particular efficacy was observed. Finally, interesting results which definitely deserve further exploration were presented in Abstract #211, which tested the combination of ipilimumab, an antibody against the cytotoxic Tlymphocyte antigen 4 (CTLA-4), with a cell-based vaccine transfected with the granulocyte macrophage colony-stimulating factor (GM-CSF) gene in advanced refractory pancreatic cancer. Though, it seems we have not yet found the culprit and the solution of this devastating disease, a small step forward might have been achieved.
Journal of the Pancreas, Mar 10, 2012
The current achievements in pancreatic cancer diagnosis and treatment are disappointing for patie... more The current achievements in pancreatic cancer diagnosis and treatment are disappointing for patients and clinicians alike. Still, in the dawn of 2012, most patients are diagnosed at a late stage where cure is not feasible, with the majority going to succumb within the same year of diagnosis. Thus, the only hope for early and diagnosis and radical treatment is the invention of diagnostic and prognostic tests which might predict accurately patients who may develop this disease and those who have the most aggressive potential, so clinician adopt the appropriate strategy. In this paper we summarize the findings from the three most interesting research abstract as presented at the 2012 American Society of Clinical Oncology Gastrointestinal Cancers Symposium. In particular, we focus on Abstract #160 which shows the diagnostic utility of microRNA serum profiling in pancreatic cancer patients, on Abstract #201 which suggests a potential prognostic role of transforming growth factor (TGF)-beta pathway in advanced pancreatic cancer, and on Abstract #165 which shows that protein S100A4 might be a new, potentially useful, predictive biomarker of gemcitabine efficacy.
JOP : Journal of the pancreas, Jan 6, 2009
Cancer pharmacogenetics is a popular and evolving field in medicine with applications in various ... more Cancer pharmacogenetics is a popular and evolving field in medicine with applications in various types of tumours helping clinicians to apply a more personalized medicine by providing information of prognostic, predictive and therapeutic value. Such evidence of pharmacogenetic applications is been already available in colon cancer (e.g. KRAS status, mismatch repair genes status, UGT1A1 polymorphisms), lung cancer (EGFR mutations, ERCC1 mutations), breast cancer (HER2/neu overexpression) and many others. In all these tumors, the genetic information is rendering the management of the involved patients safer and more effective. Interesting abstracts and announcements from the perspective of pharmacogenomics in pancreatic cancer included Abstract #4611 which suggested the use of a novel genomic study able to detect specific single nucleotide polymorphisms (SNPs) with prognostic value, Abstract #4615 which showed that the known proteins alpha1-antitrypsin and alpha1-antichymotrypsin may ...
JOP : Journal of the pancreas, Jan 10, 2013
Despite advances and investments in translation research, clinical trials and health service in g... more Despite advances and investments in translation research, clinical trials and health service in general, there is no significant impact on the survival of most patients diagnosed with advanced pancreatic adenocarcinoma. It is broadly recognized though that there is a small minority of patients who really benefit from particular treatments for reason usually not well understood. Light to this fact is gradually shed by developments in the field of pharmacogenomics, which plays pivotal role in what we call individualized medicine. In that perspective, it is of most importance to present the significant developments in pharmacogenomics announced in the recent 2013 American Society of Clinical Oncology Annual Meeting. First, the predictive role of hENT1, which codes for a gemcitabine transporter into cells, was highlighted and might help us decide whether we benefit from gemcitabine or 5-fluorouracil in the adjuvant setting (Abstract #4006). Second, authors presented the negative predict...
JOP : Journal of the pancreas, Jan 10, 2013
Over the last twenty years, there is a limited number of effective cytotoxic or biological agents... more Over the last twenty years, there is a limited number of effective cytotoxic or biological agents that managed to get approval in advanced pancreatic ductal adenocarcinoma. Despite numerous trials, investments in translational research and generally in health care, the survival of pancreatic cancer patients has improved by a few only months. This disappointing reality necessitates a better understanding of the pathogenesis of this disease and the identification of targetable alterations which might lead to development of more effective drugs or better combinations. At the 2013 Annual Meeting of the American Society of Clinical Oncology, few novel agents and new therapeutic concepts, tested in phase I studies in advanced pancreatic ductal adenocarcinoma, were presented. The first notable phase I study referred to the combination of chemotherapy with local delivery of silencing RNA against the K-ras mutation G12D, in advanced pancreatic ductal adenocarcinoma, which was well tolerated ...
JOP : Journal of the pancreas, Jan 10, 2012
Despite the enormous advances in clinical research in oncology, the prognosis of pancreatic carci... more Despite the enormous advances in clinical research in oncology, the prognosis of pancreatic carcinoma remains poor. The therapeutic options in this type of cancer are very limited, with modest results at present. In the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting, four interesting trials on the second line treatment of pancreatic cancer were presented. The first study (Abstract #4017) with a phase II design suggested that maintenance therapy with sunitinib, after a complete course of standard first line treatment, was feasible and effective while the second phase I/II study (Abstract #4034) evaluated the role of trabedersen, an agent that inhibits TGF-β2 expression. Finally, the efficacy and toxicity of lapatinib combined with either FOLFOX (Abstract #e14533) or capecitabine (Abstract #e14569) were examined in the second line setting of pancreatic cancer.
JOP : Journal of the pancreas, Jan 10, 2012
Pancreatic cancer is a relatively rare malignancy with a very aggressive natural course, not rest... more Pancreatic cancer is a relatively rare malignancy with a very aggressive natural course, not restrained by the existing current treatments. At the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting, the results of few phase I clinical studies on solid tumors and pancreatic cancer were presented. In particular, in the field of immunotherapy, a pilot phase I study tested for first time a carcinoembryonic antigen (CEA)-based vaccine (Abstract #2561) on patients with pancreatic adenocarcinoma and another one the optimal dose and efficacy of trabedersen, an inhibitor of tissue growth factor-beta 2 (TGF-β2) aiming to enhance antitumor immune responses (Abstract #4034). Other phase I studies explored the pharmacokinetic and pharmacodynamic properties of an oral gemcitabine pro-drug (LY2334737; Abstract #2554), or of the combination of gemcitabine with sirolimus (Abstract #3096) or the combination of gemcitabine with an inhibitor of mitogen-activated protein kinase (MAPK), ext...
JOP : Journal of the pancreas, Jan 10, 2012
Despite improvements in the health service and the available treatment means, the outcome of the ... more Despite improvements in the health service and the available treatment means, the outcome of the majority of patients with advanced pancreatic adenocarcinoma, even in the Western world, is disappointing. This fact necessitates invention and development of clinical and laboratory biomarkers that help us detect early enough those patients who have the worst prognosis, and who may benefit or not from our treatments and individualize thus our management accordingly. In the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting, four interesting scientific works on biomarkers in pancreatic cancer were presented. Two of them presented new clinical data such as the correlation of hand and foot skin reaction with the prognosis of patients treated with capecitabine based treatment (Abstract #4023), and the independent association of early presentation of venous thromboembolic events with poor survival (Abstract #4037). The other two significant abstracts focused on new potential pr...
Anticancer research, 2011
To assess the efficacy of gemcitabine based chemotherapy in heavily pre-treated patients with adv... more To assess the efficacy of gemcitabine based chemotherapy in heavily pre-treated patients with advanced colorectal cancer. Patients, who had been treated with gemcitabine 1250-2000 mg/m² biweekly in combination with capecitabine 1700-2000 mg/m²/day, d1-7 every two weeks were retrospectively reviewed. All the patients had previously received at least three chemotherapy regimens and 12 (55%) had also received a 4th line regimen. All the patients had been treated with a monoclonal antibody either against vascular endothelial growth factor receptor (VEGFR) or endothelial growth factor receptor (EGFR) (only if wild-type KRAS). The patients had had blood tests weekly, carcinoembryonic antigen (CEA) level measurement every 4 weeks and radiological assessment of their disease with CT scans every 8/9 weeks. Twenty two patients were included; male-female, 14:8; age ranged from 43-73 years. The majority of the patients (17/22) had performance status (PS) ECOG 0-1 and the remaining patients (5/2...
JOP : Journal of the pancreas, Jan 9, 2009
Pancreatic cancer is the fourth leading cause of cancer death in the United States and has a lowe... more Pancreatic cancer is the fourth leading cause of cancer death in the United States and has a lower survival rate than other digestive tract tumors. It remains a therapeutic challenge with limited active agents. Honing our current understanding of markers of toxicity and response, and individualizing treatment with the prognostic and therapeutic tools available are important to make a worthy impact on a patient's course. The authors summarize selected abstracts from the ASCO Gastrointestinal Cancers Symposium, San Francisco, CA, USA, January 15-17, 2009. The Symposium featured pancreatic cancer in 84 research abstracts, of which, seven are reviewed that focus on markers of toxicity: cytidine deaminase (Abstract #151) and haptogloin (Abstract #167) as markers of gemcitabine toxicity; markers of response: use of PET scan for prognosis (Abstract #157), and correlations with CA 19-9 to post-chemo-radiation resectability (Abstract #215) and time to progression (Abstract #160); and ind...
JOP : Journal of the pancreas, Jan 10, 2008
Pancreatic cancer is an international problem because of its increasing incidence worldwide. The ... more Pancreatic cancer is an international problem because of its increasing incidence worldwide. The incidence and age-adjusted mortality rates are almost equal, underscoring the aggressive nature of the disease. Although efforts are being made to unveil the principles governing the initiation and progression of this cancer, and to identify the factors that confer its particular aggressiveness, the exact succession of molecular events underlying the development of this devastating malignancy has remained unsolved. The management of pancreatic cancer is, therefore, an ongoing challenge. Many translational studies were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) this year. The author summarizes few of them including: polymorphisms of genes involved in gemcitabine metabolism correlate with prognosis in patients receiving neoadjuvant therapy for pancreatic cancer, diagnostic performance of MUC1 for pancreatic ductal adenocarcinoma, and use of whole ge...
Journal of Solid Tumors, 2012
The Pharmacogenomics Journal, 2009
The prognosis of patients with colorectal cancer (CRC) is affected by various factors at the time... more The prognosis of patients with colorectal cancer (CRC) is affected by various factors at the time of diagnosis, including location of the tumor, gender, age and overall performance status of the patient. Predicting response and limiting drug-induced toxicity for patients with CRC are also critical. Interpatient differences in tumor response and drug toxicity are common during chemotherapy. Genomic variability of key metabolic enzyme complexes, drug targets and drug transport molecules are important contributing factors. At present, there is inconsistent and rather low use of pharmacogenetic testing in the clinical setting because of a lack of robust evidence or of resources. Patients' selection and tailored treatments by the introduction of genetic testing will hopefully allow better response prediction and limit drug-induced toxicity leading to improved patient outcomes in the most cost-effective way. Here, we review the main genetic alterations observed in familial and sporadic CRC and their associations with the metabolism, efficacy and toxicities of drugs used in this disease.
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Papers by Alexios S Strimpakos