scholarly journals Making Sense of Current and Emerging Therapies in Pancreatic Cancer: Balancing Benefit and Value

2015 ◽  
pp. e222-e227 ◽  
Author(s):  
Daniel H. Ahn ◽  
Andrew H. Ko ◽  
Neal J. Meropol ◽  
Tanios S. Bekaii-Saab
Keyword(s):  
Pancreatic Cancer ◽  
Standard Of Care ◽  
The United States ◽  
Economic Effects ◽  
Making Sense ◽  
Dismal Prognosis ◽  
Emerging Therapies ◽  
Metastatic Setting ◽  
Localized Disease ◽  
New Treatments

Pancreatic cancer remains the fourth leading cause of cancer deaths in the United States with a dismal prognosis and a 5-year survival of less than 5% across all stages.1In 2014, there were approximately 46,420 new cases of pancreatic cancer with only 9% of patients having localized disease.2Given that the vast majority of patients present with advanced disease, much of the focus for drug development has been in the metastatic setting, which is evident with the advent of two combination chemotherapy regimens for this indication. Although conventional cytotoxic chemotherapy remains the standard of care, an ongoing search for novel therapeutic approaches continues. We will highlight several new approaches here, with a particular emphasis on immunotherapeutic strategies. We will also introduce concepts regarding the potential economic effects associated with the development and implementation of new treatments in pancreatic cancer.

Immunotherapy in Pancreatic Cancer

2020 ◽  
Vol 04 (04) ◽  
pp. 351-357
Author(s):  
Bassel F. El-Rayes ◽  
Mehmet Akce
Keyword(s):  
Pancreatic Cancer ◽  
Single Agent ◽  
Standard Of Care ◽  
Ongoing Research ◽  
Modest Improvement ◽  
Major Barrier ◽  
Dismal Prognosis ◽  
Rigorous Research ◽  
Tumor Mutational Burden ◽  
Immunosuppressive Tumor Microenvironment

AbstractPancreatic cancer has a dismal prognosis and is projected to be the second most common cause of cancer-related mortality by 2030. Although modest improvement in survival with current conventional cytotoxic chemotherapy-based regimens, 5-year overall survival is still 9%. Despite becoming standard of care in several malignancies, single agent or dual check point inhibitor therapy is not effective in pancreatic cancer except in subgroup of patients with high microsatellite instability or high tumor mutational burden. Profoundly immunosuppressive tumor microenvironment of pancreatic cancer is a major barrier for success of immunotherapy. Rigorous research efforts are underway to explore immune-based combination therapy with chemotherapy, radiation therapy, stroma-modifying agents, vaccines, and targeted therapies. This article aims to provide a review of the ongoing research in pancreatic cancer immunotherapy.

Updated use of first-line chemotherapy for advanced pancreatic cancer: FOLFIRINOX versus gemcitabine.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6607-6607
Author(s):  
Thomas H. Cartwright ◽  
Aimee Ginsburg Arlen ◽  
Lalan S. Wilfong ◽  
Robyn K. Harrell ◽  
J. Russell Hoverman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Advanced Pancreatic Cancer ◽  
Community Setting ◽  
Standard Of Care ◽  
The United States ◽  
Age At Diagnosis ◽  
Phase Iii ◽  
Combination Regimen ◽  
First Line ◽  
Asco 2012

6607 Background: Pancreatic cancer (PC) is the fourth leading cause of death in the United States. It is estimated that 45,220 patients will be diagnosed in 2013 and 38,460 will die (Siegel, CA Cancer J Clin 2013). Gemcitabine has long been the standard of care chemotherapy. Recent advances in treatment created a combination regimen (oxaliplatin, irinotecan, leucovorin, fluorouracil [FOLFIRINOX]) for patients with good Karnofsky performance status (PS) (Conroy, NEJM 2011). This retrospective analysis was conducted as an update to results reported at ASCO 2012 (Ginsburg Arlen, JCO 2012) to evaluate characteristics and overall survival (OS) of patients receiving FOLFIRINOX and gemcitabine-based treatments in a large outpatient community setting. This is the largest study describing FOLFIRINOX patients to date. Methods: Patients with advanced PC treated within The US Oncology Network entered into the iKnowMed (iKM) database between June 2010 and November 2012 were included. Patterns of treatment were characterized by the median age at diagnosis, sex, PS, and first-line metastatic chemotherapy prescribed. The primary endpoints of the analysis were OS and uptake of FOLFIRINOX within the network. Results: Compared to ASCO 2012 results, 1,000 additional patients were identified in iKM. Of the 1,714 total patients, 24% received FOLFIRINOX (up from 13% in 2012) and 76% gemcitabine-based therapy (87% in 2012). Increased utilization of FOLFIRINOX for patients with good PS began in June 2010. For all patients (55% male), the median age at diagnosis was 67 years and the majority (85%) had a PS of 70% or greater. The OS was significantly longer for FOLFIRINOX (9.6 mos) versus gemcitabine (6.3 mos) (p<0.0001). This held true for PS of 70% or greater patient given FOLFIRINOX (9.6 mos) versus gemcitabine (7 mos) (p<0.0001). Conclusions: Utilization of FOLFIRINOX has continued to expand after the publication of phase III trials. Our data in a community setting supports a survival advantage for FOLFIRINOX. Although the magnitude of benefit may be smaller in the community, we agree that FOLFIRINOX should become a standard of care for good PS patients.

Treatment of Metastatic Pancreatic Cancer

2005 ◽  
Vol 3 (5) ◽  
pp. 627-636 ◽  
Author(s):  
Andrew H. Ko ◽  
Margaret A. Tempero
Keyword(s):  
Pancreatic Cancer ◽  
Single Agent ◽  
Standard Of Care ◽  
The United States ◽  
Cytotoxic Agents ◽  
Metastatic Pancreatic Cancer ◽  
Fixed Dose ◽  
Fixed Dose Rate ◽  
Advanced Stages ◽  
Fixed Dose Rate Infusion

Pancreatic adenocarcinoma represents the fourth-leading cause of cancer-related mortality in the United States. The vast majority of patients are diagnosed at advanced stages of the disease when surgery is no longer an option. For these patients, systemic therapy remains the mainstay of care. Although single-agent gemcitabine has remained the standard of care since its approval in 1997, improvements in patient outcomes may potentially be realized by (1) applying pharmacokinetic principles to optimize drug delivery, such as the administration of gemcitabine at a “fixed-dose rate” infusion; (2) combining gemcitabine with other cytotoxic agents for which evidence of synergy exists, such as platinum compounds; and (3) integrating novel targeted agents such as bevacizumab, erlotinib, and cetuximab into treatment paradigms, based on an increasing understanding of the molecular pathways that govern pancreatic tumor growth and maintenance. This article provides the evidence to support each of these approaches and highlights future directions in the management of metastatic pancreatic cancer.

scholarly journals Hepatitis C Variability, Patterns of Resistance, and Impact on Therapy

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Cristina Simona Strahotin ◽  
Michael Babich
Keyword(s):  
Hepatitis C ◽  
Antiviral Agents ◽  
Cost Effective ◽  
Standard Of Care ◽  
The United States ◽  
Resistance Mechanisms ◽  
Cost Effective Method ◽  
New Treatments ◽  
Cure Rates ◽  
Effective Treatments

Hepatitis C (HCV), a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma, is the most common indication for liver transplantation in the United States. Although annual incidence of infection has declined since the 1980s, aging of the currently infected population is expected to result in an increase in HCV burden. HCV is prone to develop resistance to antiviral drugs, and despite considerable efforts to understand the virus for effective treatments, our knowledge remains incomplete. This paper reviews HCV resistance mechanisms, the traditional treatment with and the new standard of care for hepatitis C treatment. Although these new treatments remain PEG-IFN-α- and ribavirin-based, they add one of the newly FDA approved direct antiviral agents, telaprevir or boceprevir. This new “triple therapy” has resulted in greater viral cure rates, although treatment failure remains a possibility. The future may belong to nucleoside/nucleotide analogues, non-nucleoside RNA-dependent RNA polymerase inhibitors, or cyclophilin inhibitors, and the treatment of HCV may ultimately parallel that of HIV. However, research should focus not only on effective treatments, but also on the development of a HCV vaccine, as this may prove to be the most cost-effective method of eradicating this disease.

Use of first-line chemotherapy for advanced pancreatic cancer: FOLFIRINOX versus gemcitabine.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16536-e16536 ◽  
Author(s):  
Aimee Ginsburg Arlen ◽  
Thomas H. Cartwright ◽  
Lalan S. Wilfong ◽  
J. Russell Hoverman ◽  
Greg C Nelson ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Community Setting ◽  
Standard Of Care ◽  
The United States ◽  
Age At Diagnosis ◽  
Phase Iii ◽  
Combination Regimen ◽  
First Line

e16536 Background: Pancreatic cancer (PC) is the fourth leading cause of death in the United States. It is estimated that 43,920 patients will be diagnosed in 2012 and 37,390 will die (Siegel, CA Cancer J Clin, 2012). Gemcitabine has long been the standard of care chemotherapy. Recent advances in treatment options have led to the utilization of a combination regimen (oxaliplatin, irinotecan, leucovorin, fluorouracil [FOLFIRINOX]) in patients with good Karnofsky performance status (PS). This regimen was compared to single-agent gemcitabine, presented at ASCO 2010 and recently published (Conroy, NEJM, 2011). This retrospective analysis was conducted to evaluate characteristics and overall survival (OS) of patients receiving FOLFIRINOX and gemcitabine-based treatments in a large outpatient community setting. Methods: Patients with advanced PC treated within The US Oncology Network and entered into the iKnowMed (iKM) database between June 2010 and November 2011 were included. Patterns of treatment were characterized by the median age at diagnosis, sex, PS, and first-line metastatic chemotherapy prescribed. The primary endpoints of the analysis were OS and uptake of FOLFIRINOX within the network. Results: Of the 717 patients identified within the iKM database, 13% received FOLFIRINOX and 87% gemcitabine-based therapy. Increased utilization of FOLFIRINOX for patients with good PS began in June 2010. For all patients (54% male), the median age at diagnosis was 67 years and the majority of patients (89%) had a PS of 70% or greater. The OS was significantly longer for FOLFIRINOX (8.4 months) versus gemcitabine (6.4 months) (p=0.036). OS was also significantly longer for PS of 70% or greater given FOLFIRINOX (9.0 months) versus gemcitabine (6.7 months) (p=0.022). After controlling for PS, the use of gemcitabine led to a shorter OS (HR 1.4; 95% CI: 1.02-2.01). Conclusions: Utilization of FOLFIRINOX has rapidly been adopted in patients with good PS after the publication of phase III trials. Our data in a community setting supports a survival advantage for FOLFIRINOX. Although the magnitude of benefit may be smaller in the community setting, we agree that should FOLFIRINOX become a standard of care for good PS patients.

Updates in pancreatic cancer: Modest gains and hopeful targets

2018 ◽  
Vol 25 (1) ◽  
pp. 101-109 ◽  
Author(s):  
Amber Draper
Keyword(s):  
Pancreatic Cancer ◽  
Drug Targets ◽  
Systemic Disease ◽  
Tumor Biology ◽  
Standard Of Care ◽  
The United States ◽  
Incidence Rates ◽  
Delayed Presentation ◽  
Early Presentation ◽  
Cytotoxic Therapies

Pancreatic cancer is the twelfth most common cancer in the United States, representing 3.2% of all new cancer cases. While composing a small percentage of cancer diagnoses, pancreatic cancer is amongst the most lethal carcinomas, with an overall 5-year survival of 8.2% and incidence rates almost equivocal to death rates. By the time of diagnosis, a majority of patients will present with advanced stage disease. For patients with resectable disease, the estimated overall survival (OS) remains low at 20% as most will develop metastatic disease within 5 years. The lethality of this cancer is attributed to several factors including delayed presentation, lack of effective screening, and complex tumor biology and genetics. Data also suggest that even upon early presentation, pancreatic cancer is a systemic disease with micrometastasis present in the early stages. Traditional cytotoxic therapies have not been clinically impactful in pancreatic cancer, especially in advanced stages, and very little headway has been made in the development of new targeted therapies. As such, this review will discuss current advances in standard of care treatments and novel drug targets being researched.

scholarly journals Therapeutic Immunization against Glioblastoma

2018 ◽  
Vol 19 (9) ◽  
pp. 2540 ◽  
Author(s):  
Virgil Schijns ◽  
Chrystel Pretto ◽  
Anna Strik ◽  
Rianne Gloudemans-Rijkers ◽  
Laurent Deviller ◽  
...  
Keyword(s):  
Immune System ◽  
Brain Cancer ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Standard Of Care ◽  
The United States ◽  
Normal Brain ◽  
Dismal Prognosis ◽  
Medicinal Treatment ◽  
The Brain

Glioblastoma is the most common form of brain cancer in adults that produces severe damage to the brain leading to a very poor survival prognosis. The standard of care for glioblastoma is usually surgery, as well as radiotherapy followed by systemic temozolomide chemotherapy, resulting in a median survival time of about 12 to 15 months. Despite these therapeutic efforts, the tumor returns in the vast majority of patients. When relapsing, statistics suggest an imminent death dependent on the size of the tumor, the Karnofsky Performance Status, and the tumor localization. Following the standard of care, the administration of Bevacizumab, inhibiting the growth of the tumor vasculature, is an approved medicinal treatment option approved in the United States, but not in the European Union, as well as the recently approved alternating electric fields (AEFs) generator NovoTTF/Optune. However, it is clear that regardless of the current treatment regimens, glioma patients continue to have dismal prognosis and novel treatments are urgently needed. Here, we describe different approaches of recently developed therapeutic glioma brain cancer vaccines, which stimulate the patient’s immune system to recognize tumor-associated antigens (TAA) on cancer cells, aiming to instruct the immune system to eventually attack and destroy the brain tumor cells, with minimal bystander damage to normal brain cells. These distinct immunotherapies may target particular glioma TAAs which are molecularly defined, but they may also target broad patient-derived tumor antigen preparations intentionally evoking a very broad polyclonal antitumor immune stimulation.

Osteosarcoma, Chondrosarcoma, and Chordoma

2018 ◽  
Vol 36 (2) ◽  
pp. 188-193 ◽  
Author(s):  
Jeremy S. Whelan ◽  
Lara E. Davis
Keyword(s):  
Standard Of Care ◽  
High Volume ◽  
Patient Treatment ◽  
Multidisciplinary Teams ◽  
Term Survival ◽  
Therapeutic Development ◽  
Localized Disease ◽  
Multiple Challenges ◽  
New Treatments

Osteosarcoma (OS), chondrosarcoma, and chordoma are characterized by multiple challenges to the investigator, clinician, and patient. One consequence of their rarity among sarcomas, as well as their biologic and clinical heterogeneity, is that management guidelines are inadequate to inform the range of individual patient-treatment decisions from diagnosis, approaches to surgery, chemotherapy, radiotherapy, treatment of recurrence, palliative care, and quality of survivorship. Of high-grade sarcomas, OSs are among the most curable, with more than two-thirds of patients with localized disease likely to achieve long-term survival. Neoadjuvant chemotherapy comprising cisplatin, doxorubicin, and methotrexate with intercalated surgery is the standard of care for resectable OS in those younger than 40 years. Outcomes for OS presenting with unresectable metastases or recurrent disease, or in those older than 40 years are generally poor. Overall results have improved little for all patients with OS, and new treatments are needed. Surgical resection remains the cornerstone of management for chondrosarcoma and chordoma. However, the application of new biologic insights to therapeutic development indicates that improved treatments may soon be routine for patients with chondrosarcoma and chordoma for whom surgery alone is inadequate. For all these uncommon diseases, patients should be offered specialist expert care delivered by experienced multidisciplinary teams in high-volume centers.

scholarly journals Endoscopic Ultrasound-Guided Intratumoural Therapy for Pancreatic Cancer

2008 ◽  
Vol 22 (4) ◽  
pp. 405-410 ◽  
Author(s):  
Brian M Yan ◽  
Jacques Van Dam
Keyword(s):  
Pancreatic Cancer ◽  
Endoscopic Ultrasound ◽  
Standard Of Care ◽  
Current Standard ◽  
Interventional Eus ◽  
Therapeutic Modalities ◽  
Dismal Prognosis ◽  
Ablative Techniques ◽  
Fine Needle Injection ◽  
Pancreatic Cancer Therapy

Pancreatic cancer is the second most frequent gastrointestinal malignancy and carries a dismal prognosis. The current standard of care includes resection, if possible, as well as systemic chemoradiation therapy. Endoscopic ultrasound (EUS) is an established technique for the diagnosis and staging of pancreatic adenocarcinoma. Interventional EUS via fine needle injection (FNI) for the treatment of pancreatic cancer is a rapidly expanding field. The present article reviews the up-to-date developments in EUS FNI for intratumoural pancreatic cancer therapy, including antitumoural agents, immunotherapy, ablative techniques and new delivery systems. The therapeutic modalities discussed are currently under development and will hopefully reach clinical practice if benefit is demonstrated through clinical trials. EUS FNI may be an exciting new technique for the delivery of desperately needed novel therapies for pancreatic cancer.

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