287 research outputs found
Corrigendum
No full textCorrigendum to ‘Harnessing gemcitabine metabolism: a step towards personalized medicine for pancreatic cancer’ by Muhammad Saif, Yoomi Lee and Richard Kim, Therapeutic Advances in Medical Oncology 2012; 4(6):341-6. DOI: 10.1177/1758834012453755 . The corresponding author would like to note their name should be recognized as Muhammad Wasif Saif (Saif MW) and not as Muhammad Saif (Saif M) in this article
Current use and potential role of bevacizumab in the treatment of gastrointestinal cancers
No full textJia Li, Muhammad Wasif SaifYale Cancer Center, Yale School of Medicine, New Haven CT, USAAbstract: Angiogenesis is essential for cancer growth and metastasis. Vascular endothelial growth factor (VEGF) is a key modulator of angiogenesis. In addition, overexpression of VEGF is correlated with advanced disease and poor prognosis. Bevacizumab, a recombinant humanized anti-VEGF monoclonal antibody, is the first anti-angiogenic agent approved by Food and Drug Administration for use in treatment of human solid cancers. Although bevacizumab has received most attention for first-line treatment of advanced colorectal and nonsmall-cell lung cancer, there is a rapidly growing body of evidence for its efficacy in treatment of a number of other solid tumors. We present the current status and potential use of bevacizumab therapy in gastrointestinal cancers.Keywords: advanced colon cancer, angiogenesis, bevacizumab, chemotherapy, metastatic, targeted therapy, vascular endothelial growth factor, gastric cancer, pancreatic cancer, hepatocellular cance
Anti-VEGF agents in metastatic colorectal cancer (mCRC): are they all alike?
No full textMuhammad Wasif Saif GI Oncology Program, Tufts University School of Medicine, Boston, MA, USA Abstract: Bevacizumab is a monoclonal antibody that binds and neutralizes vascular endothelial growth factor (VEGF)-A, a key player in the angiogenesis pathway. Despite benefits of bevacizumab in cancer therapy, it is clear that the VEGF pathway is complex, involving multiple isoforms, receptors, and alternative ligands such as VEGF-B, and placental growth factor, which could enable escape from VEGF-A-targeted angiogenesis inhibition. Recently developed therapies have targeted other ligands in the VEGF pathway (eg, aflibercept, known as ziv-aflibercept in the United States), VEGF receptors (eg, ramucirumab), and their tyrosine kinase signaling (ie, tyrosine kinase inhibitors). The goal of the current review was to identify comparative preclinical data for the currently available VEGF-targeted therapies. Sources were compiled using PubMed searches (2007 to 2012), using search terms including, but not limited to: “bevacizumab,” “aflibercept,” “ramucirumab,” and “IMC-18F1.” Two preclinical studies were identified that compared bevacizumab and the newer agent, aflibercept. These studies identified some important differences in binding and pharmacodynamic activity, although the potential clinical relevance of these findings is not known. Newer antiangiogenesis therapies should help further expand treatment options for colorectal and other cancers. Comparative preclinical data on these agents is currently lacking. Keywords: aflibercept, antiangiogenesis, metastatic colorectal cancer (mCRC), tyrosine kinase inhibitor (TKI), vascular endothelial growth factor (VEGF
Mitomycin-Induced Interstitial Pneumonitis in a Patient with BRCA2 Associated Metastatic Pancreatic Carcinoma
No full textNo abstract available.Image: Space-filling model of the mitomycin molecule (Author: Jynto (talk); Wikimedia Commons
Sorafenib-Induced Acute Pancreatitis
No full textNo abstract available.Image: Sorafenib BRAF labeled (Author: Nhevitt; Wikimedia Commons
Management of a Patient with Metastatic Colorectal Cancer and Liver Metastases
No full textLiver metastases are commonly encountered in patients presenting with metastatic colorectal cancer (mCRC); resection is the treatment of choice. A number of systemic treatment options are currently available for such patients, including the use of 5-fluorouracil-based chemotherapies and oxaliplatin (e.g., FOLFOX) in combination with biologic agents that target angiogenesis (e.g., bevacizumab). For patients with progression following first-line treatment, current second-line options include a change in chemotherapy with bevacizumab (for patients who did or did not receive prior bevacizumab) or FOLFIRI in combination with aflibercept, a more recently approved antiangiogenesis therapy. Neurotoxicity is a well-established adverse event of oxaliplatin-based therapy. The current case details an mCRC patient with liver metastases who was treated with a capecitabine and oxaliplatin regimen (XELOX), and experienced two episodes of transient cortical blindness possibly related to oxaliplatin. After disease progression, the patient was switched to a regimen of FOLFIRI and aflibercept and did well on this second-line regimen
Adjuvant Therapy of Pancreatic Cancer: Beyond Gemcitabine
No full textThere is no consensus on what constitutes “standard” adjuvant therapy for pancreatic cancer. This controversy derives from several studies, each fraught with its own limitations. Standards of care also vary somewhat on the geography as chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America (GITSG, RTOG) while chemotherapy alone is the current standard in Europe (ESPAC-1, CONKO, ESPAC-3). The high rate of locoregional failure following surgical resection for adenocarcinoma of the pancreas has made it clear that some form of adjuvant therapy should be considered in these patients. A phase II study was presented at the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium to assess the effect of the addition of algenpantucel-L immunotherapy to standard adjuvant therapy on survival in patients with resected pancreas cancer (Abstract #236). The author reviews the abstract in the context of our previous knowledge.Image: Hyperacute rejection and immunotherapeutic applications
Updates in Adjuvant Therapy in Pancreatic Cancer: Gemcitabine and Beyond
No full textPancreatic cancer represents the 4th leading cause of cancer deaths in the United States. Surgical resection remains the only potential curative approach. However, given the notion of a high recurrence rate, adjuvant therapy is needed to offset this risk. The 2010 American Society of Oncology Gastrointestinal Cancers Symposium offered new insights into optimized approaches towards adjuvant therapy of pancreatic cancer. Abstracts focusing on the role of targeted therapy utilizing erlotinib or GI-4000 in combination with gemcitabine (Abstracts #224 and #229) were presented. Subbiah, et al. presented a retrospective analysis comparing systemic chemotherapy versus chemoradiotherapy (Abstract #230) in the adjuvant setting. In addition, a data driven prediction tool to help predict which patients would be able to complete a course of adjuvant therapy in order to select out those who may alternative approaches (Abstract #236) was also presented. The authors summarize these findings presented at the 2010 ASCO Gastrointestinal Cancers Symposium, January 22-24, 2010, Orlando, FL, USA.Image: Chemical structure of gemcitabine (Author: Calvero, Wikimedia Comons
Novel Drug Targets Based on Association between Inflammation and Pancreatic Ductal Adenocarcinoma
No full textNo abstract available.Image: Yale University School of Medicine. New Haven, CT, USA
Advancements in the Management of Pancreatic Cancer: 2013
No full textPancreatic cancer still remains a significant, unresolved therapeutic challenge and is the most lethal type of gastrointestinal cancer with a 5-year survival rate of 5%. Adjuvant chemotherapy remains to be gemcitabine alone, though fluorouracil offers the same survival and role of radiation remains controversial. Nevertheless, only a few patients survive for at least 5 years after R0 resection and adjuvant therapy. Borderline resectable pancreatic cancer remains an area that requires multi-disciplinary approach. Neo-adjuvant therapy very likely plays a role to downstage to a resectable state in these subgroup patients. There are different treatment approaches to locally advanced pancreatic cancer management, including single or multi-agent chemotherapy, chemotherapy followed by chemoradiation, or immediate concurrent chemoradiation. Most patients need palliative treatment. Once pancreatic cancer becomes metastatic, it is uniformly fatal with an overall survival of generally 6 months from time of diagnosis. Gemcitabine has been the standard since 1997. FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan, leucovorin) has already shown superiority over gemcitabine in both progression-free survival and overall survival, but this regimen is suitable only for selected patients in ECOG performance status 0-1. FOLFIRINOX has already trickled down to the clinic in various modifications and in different patient groups, both locally advanced and metastatic. Many targeted agents, including bevacizumab, cetuximab showed negative results, except mild benefit with addition of erlotinib with gemcitabine, which was not considered clinically significant. There is no consensus regarding treatment in the second-line setting. It will be true to say that there was a real medical breakthrough with regards to improving the prognosis of pancreatic cancer as of 2013 with the results of MPACT study. In this study, patients who received nab-paclitaxel plus gemcitabine lived a median of 8.5 months, compared with 6.7 months for those who received gemcitabine alone. At the end of one year, 35% of those getting nab-paclitaxel were alive, compared with 22% of those getting only gemcitabine. After two years, the figures were 9% for those getting nab-paclitaxel and 4% for those who received gemcitabine.Image: The "Project Purple Pancreatic Cancer Research Fund" established by Tufts Medical Center. Boston, MA, USA
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