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Introduction: Pancreatic cancer is a highly aggressive and lethal malignancy, with a particularly poor prognosis and limited treatment options, especially after development of gemcitabine-refractory disease. Nanoliposomal irinotecan (MM-398), is a novel formulation of irinotecan hydrochloride (CPT-11), exhibiting improved pharmacokinetic properties and bio-distribution to the tumor tissue in comparison to free-form irinotecan. MM-398, in combination with 5-fluorouracil (5-FU) and folinic acid (FA), is the first regimen approved by the Food and Drug Administration (FDA) as a second-line treatment in pancreatic cancer, following failure of gemcitabine-based induction chemotherapy.Areas covered: A critical overview of the pharmacology, clinical efficacy and toxicity of MM-398 in pancreatic cancer is herein presented and discussed within the context of currently available treatment strategies as well as in light of future perspectives in this field.Expert opinion: Incorporation of MM-398 as a second-line agent in routine clinical management of pancreatic cancer patients represents a breakthrough step forward in the treatment of this challenging disease. Future preclinical and clinical research should help delineate more clearly the full potential and limitations of this novel drug in pancreatic cancer therapeutics, disclose its potential synergies or interactions with other anticancer agents or regimens, and identify novel biomarkers for a more accurate prediction of its efficacy and toxicity. © 2016Informa UK Limited, trading as Taylor & Francis Group.

Neuroendocrine tumors are a rare and heterogeneous group of tumors with a variety of primary origins and variable aggressiveness. Platinum-based chemotherapy has been the cornerstone of treatment for the poorly differentiated tumors. However, well-differentiated neuroendocrine tumors are quite chemoresistant and therapy options are limited. Octreotide analogs and tyrosine kinase inhibitors are widely acceptable treatments due to substantial efficacy and tolerable toxicity. On the contrary, monotherapy or combinations of the only approved cytotoxic agent streptozocin with other drugs have been almost abandoned because of excessive toxic events. In recent years, the combination of capecitabine and temozolomide has emerged as the most promising and efficacious treatment. The oral route of administration and the substantial improvement in the outcomes with manageable toxicity are the major advantages. We reviewed the current literature and presented the profile of the capecitabine/temozolomide combination in the management of well-differentiated neuroendocrine tumors. © 2016 Kotteas et al.

Cancer of the exocrine pancreas is a malignancy with a high lethal rate. Surgical resection is the only possible curative mode of treatment. Metastatic pancreatic cancer is incurable with modest results from the current treatment options. New genomic information could prove treatment efficacy. An independent review of PubMed and Science Direct databases was performed up to March 2016, using combinations of terms such pancreatic exocrine cancer, chemotherapy, genomic profile, pancreatic cancer pharmacogenomics, genomics, molecular pancreatic pathogenesis, and targeted therapy. Recent genetic studies have identified new markers and therapeutic targets. Our current knowledge of pancreatic cancer genetics must be further advanced to elucidate the molecular basis and pathogenesis of the disease, improve the accuracy of diagnosis, and guide tailor-made therapies. © 2016 Hellenic Society of Gastroenterology.

Pancreatic cancer is an aggressive malignancy with a poor overall survival rate. Given advances in pharmacogenomics, numerous gene mutations have been identified that could be potential targets for drug development. Therefore, future research strategies may identify prognostic and predictive markers aiming to improve outcome by maximizing efficacy whilst lowering toxicity. In this commentary, we summarize several interesting results regarding pancreatic cancer pharmacogenetics that have been presented in the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting. In particular, we focus on Abstract #4124, which investigated the potential predictive role of human equilibrative nucleoside transporter 1 (hENT1) in patients treated with adjuvant gemcitabine for pancreatic cancer, on Abstract #4125, which examined the tolerability of a modified FOLFORINOX study based on UGT1A1*28 genotype guided dosing of IRI in patients with advanced pancreatic cancer, and on Abstract #4130, which confirmed the predictive role of circulating tumor and invasive cells (CTICs) from patients with unresectable pancreatic cancer in second-line chemotherapy treatment setting.

Ampullary carcinomas are rare malignancies representing less than 1% of all gastrointestinal cancers. Given the low incidence rate, there is scarcity of data regarding the survival benefit of the treatment options available. In the 2014 ASCO Gastrointestinal Cancers Symposium there were two abstracts that discussed the role of pancreaticoduodenectomy and adjuvant radiation therapy in ampullary carcinoma. The first study (Abstract #366) demonstrated a decline in morbidity and mortality over time for pancreaticoduodenectomy making it a reasonable option for successful treatment of ampullary carcinoma. The second study (Abstract #282) showed that adjuvant radiation therapy in patients with T2 tumors had improved median survival times compared to patients that did not receive radiation therapy.

QOL is highly affected in individuals suffering from pancreatic cancer. One parameter that influences negatively QOL in these patients is cancer -cachexia syndrome. During the ASCO Annual Meeting 2014, one abstract focusing on cancer-cachexia syndrome (Abstract #15208) emphasized the fact that cachexia is under diagnosed even in patients with pancreatic cancer who constitute a high-risk group for presenting this syndrome. In addition the abstract raises concerns about the benefit of the use of dronabinol and megestrol acetate in treating the cachexia syndrome in this group of patients. Another important factor that determines QOL in pancreatic cancer patients is surgical procedures-pancreatectomies that these patients may undergo. A very interesting abstract presented also at the ASCO Annual Meeting 2014 (Abstract #15234) explores the benefit of using pasireotide perioperative in ameliorating QOL of patients who had surgical intervention.

Pancreatic cancer marked significant increase of incidence during the last decades in the elderly population. Despite the certain increase of incidence there are no international guidelines for elderly patients who are suffering from pancreatic cancer. During the ASCO Annual Meeting 2014, two abstracts focusing on elderly patients suffering from different histological types of pancreatic cancer were presented. The first retrospective study (Abstract # 4119) showed the benefit of the systemic treatment on overall survival for elderly patients with stage IV pancreatic adenocarcinoma. The second retrospective study (Abstract # 4112) demonstrates the positive effect of somatostatin analogue (octreotide-LAR) treatment on overall survival for elderly patients with neuroendocrine pancreatic carcinoma.

Pancreatic cancer represents one of the leading causes of cancer related deaths worldwide and constitutes a major public health problem. Despite the advances in diagnosis and treatment, the overall five-year survival remains low, thus leading the focus of medical research towards the identification and modification of potential risk factors. This year, in ASCO Annual Meeting two interesting studies were presented. Ghani et al. (abstract #e15183) sought to investigate the effect of smoking on chemotherapy response in patients with metastatic pancreatic cancer, while Walker et al. (abstract #4117) presented the results of their study regarding the effect of statin use in the prevention of pancreatic cancer. Both studies concluded to useful results that along with the existing literature may further stimulate medical research towards better recognition of risk factors and the application of this knowledge in the clinical practice.

Therapeutic options for locally advanced pancreatic cancer (LAPC) include concurrent chemoradiation, induction chemotherapy followed by chemoradiation or systemic therapy alone. The original Gastro-Intestinal Study Group and Eastern Cooperative Oncology Group studies defined fluorouracil (5-FU) with concurrent radiation therapy followed by maintenance 5-FU until progression, as the standard therapy for this subset of patients. Although this combined therapy has been demonstrated to increase local control and median survival from 8 to 12 months, almost all patients succumb to the disease secondary to either local or distant recurrence. Our earlier studies provided a strong rationale for the use of capecitabine in combination with concurrent radiation followed by maintenance capecitabine therapy. To report our clinical experience, we retrospectively evaluated our patients who were treated with maintenance capecitabine. We reviewed the medical records of patients with LAPC who received treatment with capecitabine and radiation, followed by a 4-week rest, then capecitabine alone 1,000 mg twice daily (ECOG performance status 2 or age >70 years) or 1,500 mg twice daily for 14 days every 3 weeks until progressive disease. We treated 43 patients between September 2004 and September 2012. The population consisted of 16 females and 25 males, with a median age of 64 years (range, 38-80 years). Patients received maintenance capecitabine for median duration of 9 months (range, 3-18 months). The median overall survival (OS) for these patients was 17 months, with two patients still living and receiving therapy. The 6-month survival rate was 91% (39/43), 1-year survival rate was 72% (31/43) and 2-year OS rate was 26% (11/43). Grade 3 or 4 toxicity was observed rarely: Hand-foot syndrome (HFS) in two patients, diarrhea in one patient and peripheral neuropathy in one patient, and there was no mortality directly related to treatment. Capecitabine maintenance therapy following chemoradiation in LAPC offers an effective, tolerable and convenient alternative to 5-FU. To the best of our knowledge, this is the largest study of its kind which has determined the safety and efficacy of capecitabine maintenance therapy for patients with LAPC.

Introduction: Oxaliplatin, has become an integral part of the medical treatment of colorectal cancer and other malignancies. Increased use of the drug during the last decade, has led to increased occurrence of oxaliplatin-induced hypersensitivity reactions (HSRs), posing a significant challenge for clinicians. This article aims to review the existing literature regarding the incidence, clinical presentation, pathophysiology, risk factors and current management of oxaliplatin-induced HSRs. Areas covered: A systematic review of the English literature published in PubMed and Medline was undertaken. The clinical manifestations of HSRs were found to be variable and unpredictable. These reactions should be an important concern, as their potential life-threatening risks can force doctors to stop treatment and seek alternatives, which may be less effective, not as well tolerated and/or more expensive. There are a few strategies to prevent these reactions so that patients can still benefit from oxaliplatin. Such strategies include the use of premedication (steroid and antagonists of type I and II histamine receptors), prolonged infusion time and desensitization. Expert opinion: The presented management strategies as well as novel diagnostic tools including skin/intradermal tests and specific IgE have shown promising results. However, future research and validation are warranted in bigger clinical trials. © 2014 Informa UK, Ltd.

Neuroendocrine tumors (NET) of the pancreas are uncommon neoplasms that arise from the pancreatic islet cells. Surgical resections are being tested, as well as multiple chemotherapy agents. Current treatment options for nonresectable disease include somatostatin analogs and chemotherapy. New therapies focus on specific molecular targets such as sunitinib, angiogenesis inhibitor, that target vascular endothelial growth factor receptor (VEGFR) and other growth factor receptors and everolimus, an inhibitor of the mammalian target of rapamycin. Functionally based medical therapies for NET include somatostatin analogs to control symptoms. The 2014 annual meeting of American Society of Clinical Oncology (ASCO) brought us new insights into the management of pancreatic neuroendocrine tumors. The focus of this review will serve to highlight specific Abstracts (#e15160 and #e15161), that shed light on new therapeutic options that help target the unique pathways of this malignancies.

In the field of treatment of pancreatic cancer, there has been significant progress lately. After the ACCORD/PRODIGE-4 study, 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) became the standard combination for first-line chemotherapy. This led also to its use in the neoadjuvant setting in borderline resectable tumors, or locally advanced unresectable disease, improving the resectability and survival. The major disadvantage of this therapy is increased toxicity, limiting its use to young patients with no comorbidities. This arises the need to make dose reductions in clinical practice, with a possible drawback in effectiveness. The authors summarize three Abstracts (#256, #275, #305) presented at the 2014 ASCO Gastrointestinal Cancers Symposium which were focused in the use of modified forms of FOLFIRINOX, their toxicity profile and effectiveness. Reduced toxicity was observed, without affecting the effectiveness of the combination.

Pancreatic cancer is one of the leading causes of cancer deaths worldwide and constitutes a major public health problem. One of the most common symptoms associated with pancreatic adenocarcinoma is jaundice, caused by the obstruction of common bile duct. Endobiliary stenting is used to relief these patients either preoperatively or merely for palliation and plastic or metal stents are usually endoscopically or percutaneously placed. Two interesting studies were presented at the 2014 ASCO Gastrointestinal Cancers Symposium. Strom et al. sought to investigate the effect of preoperative biliary drainage on recurrence and survival and they concluded that percutaneous biliary decompression was an independent predictor of worse overall survival and was associated with non-significant increase in hepatic recurrence (Abstract #314). Montero et al. presented the results of their study regarding the cost-effectiveness of metal stents in patients with inoperable pancreatic cancer and they concluded that placement of metal biliary stents is cost saving, improves overall survival and quality-adjusted survival compared with plastic stents (Abstract #260). Both studies concluded to useful results that along with the existing literature and formulated guidelines may help the provision of more effective, higher quality management of these patients.

Pancreatic cancer is a lethal disease and its prognosis remains dismal. The modest results of existing available treatments in the first line setting reveal the need of new therapeutic strategies. In this year's American Society of Clinical Oncology (ASCO) Annual Meeting four remarkable studies were presented regarding this vulnerable group of patients. The efficacy and toxicity profile of gemcitabine plus erlotinib plus capecitabine (Abstract #4122), refametinib plus gemcitabine (Abstract #4025), gemcitabine plus docetaxel plus capecitabine plus cisplatin (Abstract #4135) were examined and the predictive value of a biomarker panel testing response to gemcitabine with or without the addition of erlotinib (Abstract #4133) was also presented.

Background. Pancreatic tumors are rare and could arise from either the exocrine (ductal and acinar cells) or the endocrine (neuroendocrine cells) components of the pancreas. In some instances, the occurrence of pancreatic tumors comprising both acinar cells and neuroendocrine cells, with neuroendocrine cells making up more than 30% of the tumor, has been identified. This unique entity has been referred to as mixed acinar-neuroendocrine carcinoma (MANEC). Only about 20 such cases have been reported in the literature. Case Report. We report an interesting case of MANEC with neuroendocrine cell predominance in a woman presenting with epigastric pain secondary to a pancreatic mass with acinar and endocrine differentiation. She underwent surgical resection of the tumor and was offered adjuvant treatment chemotherapy with carboplatin, etoposide, and radiotherapy for positive tumor resection margins. Conclusions. Given the paucity of the cases of MANEC, continuous reporting of these cases when identified should be encouraged to aid oncologists in understanding the disease and help establish standardized management. © 2013 Onyekachi Henry Ogbonna et al.

The hallmark of pancreatic tumours, the desmoplastic reaction, provides a unique microenvironment that affects pancreatic tumour behaviour, its ability to grow and metastasize as well as resist the effects of chemotherapy. Complex molecular interactions and pathways give rise to the desmoplastic reaction. Breakdown or penetration of the desmoplastic reaction may hold the key to overcoming the limits of delivery of efficacious chemotherapy or the development of new targeted treatments. Herein we discuss such new developments to fight the desmoplastic reaction, including inhibitors of the epidermal growth factor, fibroblast growth factor, the hedgehog pathway, as well as new molecular targets like CD40 agonist and its effects on T cells, extracellular matrix modifying enzymes such as LOXL2 inhibitor and novel tumour penetrating peptides for delivery of drugs. © 2012 E. E. Merika et al.

Lung cancer is the primary cause of cancer-related mortality worldwide and although improvements in treatment have been achieved over the last few years, long-term survival rates for lung cancer patients remain poor. Therefore, there is an imperative need for molecularly targeted agents that will achieve long-term disease control. Numerous downstream molecular pathways, such as EGF/RAS/RAF/MEK/ERK and PI3K/AKT/mTOR are identified as having a key role in the pathogenesis of various forms of human cancer, including lung cancer. PI3K/AKT/mTOR signal pathway is an important intracellular signal transduction pathway with a significant role in cell proliferation, growth, survival, vesicle trafficking, glucose transport, and cytoskeletal organization. Aberrations in many primary and secondary messenger molecules of this pathway, including mutations and amplifications, are accounted for tumor cell proliferation, inhibition of apoptosis, angiogenesis, metastasis and resistance to chemotherapy-radiotherapy. In this review article, we investigate thoroughly the biological role of PI3K pathway in lung cancer and its contribution in the development of future therapeutic strategies. © 2012 by the authors; licensee MDPI, Basel, Switzerland.

Mutations in the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene are a well-described mechanism of resistance to monoclonal antibodies that target the epidermal growth factor receptor in patients with metastatic and nonoperable colorectal cancer. Treatment options in this population are limited to conventional chemotherapy regimens and antiangiogenesis compounds. Numerous strategies have been proposed in preclinical models as being effective in the presence of KRAS mutations. As basic and translational research further unravels the complex interactions and regulation points in the pathways downstream of epidermal growth factor receptor, more drugs become available for clinical testing. Indeed, there are many ongoing clinical trials that focus on the safety and efficacy of novel compounds in patients with KRAS-mutated colorectal cancer. This is a review of the literature with regard to the rationale of various approaches on this topic and also a summary of the current active clinical trials limited to patients with KRAS-mutated colorectal cancer. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Despite recent advances in diagnosis and treatment of certain cancers such as breast, colon and prostate cancers, pancreatic cancer remains a deadly malignancy with a mortality rate almost equal to its incidence. The survival benefit after all possible medical interventions is still disappointing for the majority of patients with pancreatic cancer. Improving the quality of life and increasing survival remain as the key objectives of pharmacogenomics and clinical investigation in pancreatic cancer. There are several notable genetic loci (e.g., RRM1, CDA, DPYD, UGT1A1) known to predict the toxicity of drugs used in pancreatic cancer such as gemcitabine, capecitabine, platinum agents and irinotecan. Other genes are associated with efficacy of these drugs (e.g., HuR, DCK, TS, ERCC1), although prospective validation of their clinical utility is still required. This paper presents the latest research advances in pharmacogenomics of pancreatic cancer with a view to molecular guidance for clinical diagnosis and individualized patient care. © 2010 Bentham Science Publishers Ltd.

Summary Background Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness. Methods In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing. Findings Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57–76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53–2·21), male sex (1·63, 1·07–2·48), smoking status (former smoker vs never smoked: 1·60, 1·03–2·47), number of comorbidities (two vs none: 4·50, 1·33–15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11–7·18), active cancer (progressing vs remission: 5·20, 2·77–9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79–4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07–0·84) or the US-Midwest (0·50, 0·28–0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality. Interpretation Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments. Funding American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.