Gastrointestinal Cancer

Loss of two hormones creates a 'recipe for colon cancer'

In a prospective case-control study, individuals in the lowest quartile of circulating insulin-like growth factor binding protein -1 (IGFBP-1) had a twofold greater risk of developing pancreatic cancer than those in the three highest quartiles

Targeted Rx for pancreatic cancer

New animal studies show that the loss of two hormones plays a significant role in the development of colon cancer. If confirmed, the discovery "converts colon cancer from a genetic disease, which is the way we've all thought about it, to a disease of hormone insufficiency,"

Diagnostic Dilemma: GI Disease

An experimental gene therapy targeting pancreatic cancer reduced or eradicated tumors, inhibited metastasis, and prolonged survival in experiments in two mouse models, and did so with very limited toxicity.

Shivani Sood, MD, MPH;Jennifer Leong, MD;Matthew J. Mckinley, MD

Superselective chemo strategies for HCC

This photograph is from an upper gastrointestinal endoscopy on a 15-year-old male. He has a history of a total colectomy and is being evaluated for iron deficiency anemia. He denies abdominal pain, weight loss, and melena. He notes occasional bright red blood on the toilet paper but denies hematochezia.

Colon cancer trial of Vectibix is recruiting

Delivery of chemotherapy to hepatic artery branches that only or mainly feed a tumorso-called superselective chemoembolization and chemoinfusionyields favorable outcomes in patients with hepatocellular carcinoma (HCC)

Don't Interrupt Imatinib in GIST Patients

Amgen is currently enrolling patients in a phase III study designed to evaluate the effectiveness of panitumumab (Vectibix) in combination with chemotherapy (FOLFIRI)

Avalon initiates phase II trial of AVN944 in pancreatic cancer

Interrupting imatinib (Gleevec) therapy in advanced gastrointestinal stromal tumor (GIST) patients who have had a long-lasting response results in a high risk of rapid progression, according to results of a clinical trial (BFR14) presented at the American Society of Clinical Oncology 43rd Annual Meeting

Nab-rapamycin active in breast and colon cancer models

Avalon initiates phase II trial of AVN944 in pancreatic cancer

Key Developments in Rectal Cancer Treatment

Nanoparticle albumin-bound (nab) rapamycin (ABI-009) showed antitumor activity in xeno-graft models of breast and colon cancer, according to investigators from Abraxis BioScience

Bruce D. Minsky, MD

Hepatocellular Carcinoma: Neoadjuvant Therapy Reconsidered

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are often overexpressed in colorectal cancer and are associated with inferior outcomes. Based on successful randomized phase III trials, anti-EGFR and anti-VEGF therapeutics have entered clinical practice. Cetuximab (Erbitux), an EGFR-specific antibody, is currently approved in the United States in combination with irinotecan (Camptosar) for patients with metastatic colorectal cancer refractory to irinotecan or as a single agent for patients unable to tolerate irinotecan-based therapy. In retrospective analyses, patients with EGFR-expressing rectal cancer undergoing neoadjuvant radiation therapy had a significantly inferior disease-free survival and lower rates of achieving pathologic complete response. Based on the positive data in metastatic colorectal cancer and synergy with radiation therapy seen in preclinical models, there is a strong rationale to combine cetuximab with neoadjuvant radiation therapy and chemotherapy in rectal cancer. Bevacizumab (Avastin), a VEGF-specific antibody, was the first antiangiogenic agent to be approved in the United States for use in combination with standard chemotherapy in the first- and second-line of treatment in metastatic colorectal cancer. VEGF-targeted therapy may lead to indirect killing of cancer cells by damaging tumor blood vessels, and may increase the radiosensitivity of tumor-associated endothelial cells. VEGF blockade can also "normalize" tumor vasculature, thereby leading to greater tumor oxygenation and drug penetration. This review will address completed and ongoing trials that have established and continue to clarify the effects of these agents in rectal cancer.

Sunil K. Geevarghese, MD;Ravi S. Chari, MD

Honing Therapy for Rectal Cancer

Hepatocellular carcinoma (HCC) is an aggressive tumor that often occurs in the setting of chronic liver disease and cirrhosis. The incidence of hepatocellular carcinoma is increasing in the United States and worldwide. Orthotopic liver transplantation (OLT) is a viable and potentially curative option for selected patients with HCC. Locoregional therapy has been used to control HCC before transplantation because of the limited number of donor organs, to prevent tumor progression, and to decrease the incidence of dropouts from the transplant waiting list. Traditionally, multiple investigational locoregional modalities such as tumor resection, radiofrequency ablation, transarterial chemoembolization, and systemic chemotherapy have been used as "bridging" therapies. While the investigation of novel neoadjuvant treatments is justified in an effort to prevent tumor progression, the absence of randomized controlled trials leaves uncertainty about the utility of these maneuvers in improving outcome. This review summarizes the current data on the different modalities used worldwide in the neoadjuvant treatment of hepatocellular carcinoma, the rationale for these approaches, efficacy, potential complications, and future prospects.

Matthew Callister, MD;Leonard L. Gunderson, MD, MS

Hepatocellular Carcinoma Patients Awaiting Transplant: General Guidelines for Management

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are often overexpressed in colorectal cancer and are associated with inferior outcomes. Based on successful randomized phase III trials, anti-EGFR and anti-VEGF therapeutics have entered clinical practice. Cetuximab (Erbitux), an EGFR-specific antibody, is currently approved in the United States in combination with irinotecan (Camptosar) for patients with metastatic colorectal cancer refractory to irinotecan or as a single agent for patients unable to tolerate irinotecan-based therapy. In retrospective analyses, patients with EGFR-expressing rectal cancer undergoing neoadjuvant radiation therapy had a significantly inferior disease-free survival and lower rates of achieving pathologic complete response. Based on the positive data in metastatic colorectal cancer and synergy with radiation therapy seen in preclinical models, there is a strong rationale to combine cetuximab with neoadjuvant radiation therapy and chemotherapy in rectal cancer. Bevacizumab (Avastin), a VEGF-specific antibody, was the first antiangiogenic agent to be approved in the United States for use in combination with standard chemotherapy in the first- and second-line of treatment in metastatic colorectal cancer. VEGF-targeted therapy may lead to indirect killing of cancer cells by damaging tumor blood vessels, and may increase the radiosensitivity of tumor-associated endothelial cells. VEGF blockade can also "normalize" tumor vasculature, thereby leading to greater tumor oxygenation and drug penetration. This review will address completed and ongoing trials that have established and continue to clarify the effects of these agents in rectal cancer.

Promising Early Results With Capsule Endoscopy for Colon Cancer Screening

Hepatocellular carcinoma (HCC) is an aggressive tumor that often occurs in the setting of chronic liver disease and cirrhosis. The incidence of hepatocellular carcinoma is increasing in the United States and worldwide. Orthotopic liver transplantation (OLT) is a viable and potentially curative option for selected patients with HCC. Locoregional therapy has been used to control HCC before transplantation because of the limited number of donor organs, to prevent tumor progression, and to decrease the incidence of dropouts from the transplant waiting list. Traditionally, multiple investigational locoregional modalities such as tumor resection, radiofrequency ablation, transarterial chemoembolization, and systemic chemotherapy have been used as "bridging" therapies. While the investigation of novel neoadjuvant treatments is justified in an effort to prevent tumor progression, the absence of randomized controlled trials leaves uncertainty about the utility of these maneuvers in improving outcome. This review summarizes the current data on the different modalities used worldwide in the neoadjuvant treatment of hepatocellular carcinoma, the rationale for these approaches, efficacy, potential complications, and future prospects.

The Role of Integrins in Colorectal Cancer

Capsule endoscopy may eventually rival colonoscopy for the detection of colon polyps, according to the leaders of an ongoing clinical trial comparing the two technologies.

Christophe Le Tourneau, MD;Sandrine Faivre, MD, PhD;Eric Raymond, MD, PhD

Targeted Therapy in Rectal Cancer

Integrins have direct effects in stimulating proliferation and preventing apoptosis in cancer cells and mediating proangiogenic interactions between endothelial cells and extracellular matrix. Alterations of expression of various integrins and their receptors have been observed in various cancers in which angiogenesis is known to play a role, including colorectal cancer. Inhibition of specific integrins might thus inhibit both direct effects of integrins on cancer cells and tumor angiogenesis. Inhibitory peptides and anti-integrin monoclonal antibodies are currently being investigated in clinical trials in patients with solid tumors, with early evidence suggesting clinical benefit in disease stabilization with use of an anti-αvβ3 antibody in the settings of colorectal cancer, renal cell carcinoma, and melanoma. Integrin inhibition alone and with other targeted therapeutic approaches should be further investigated in clinical trials in patients with colorectal cancer.

Christopher G. Willett, MD;Dan G. Duda, Dmd, PhD;Brian G. Czito, MD;Johanna C. Bendell, MD;Jeffrey W. Clark, MD;Rakesh K. Jain, PhD

Therapeutic Options in Gastric Cancer: Neoadjuvant Chemotherapy vs Postoperative Chemoradiotherapy

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are often overexpressed in colorectal cancer and are associated with inferior outcomes. Based on successful randomized phase III trials, anti-EGFR and anti-VEGF therapeutics have entered clinical practice. Cetuximab (Erbitux), an EGFR-specific antibody, is currently approved in the United States in combination with irinotecan (Camptosar) for patients with metastatic colorectal cancer refractory to irinotecan or as a single agent for patients unable to tolerate irinotecan-based therapy. In retrospective analyses, patients with EGFR-expressing rectal cancer undergoing neoadjuvant radiation therapy had a significantly inferior disease-free survival and lower rates of achieving pathologic complete response. Based on the positive data in metastatic colorectal cancer and synergy with radiation therapy seen in preclinical models, there is a strong rationale to combine cetuximab with neoadjuvant radiation therapy and chemotherapy in rectal cancer. Bevacizumab (Avastin), a VEGF-specific antibody, was the first antiangiogenic agent to be approved in the United States for use in combination with standard chemotherapy in the first- and second-line of treatment in metastatic colorectal cancer. VEGF-targeted therapy may lead to indirect killing of cancer cells by damaging tumor blood vessels, and may increase the radiosensitivity of tumor-associated endothelial cells. VEGF blockade can also "normalize" tumor vasculature, thereby leading to greater tumor oxygenation and drug penetration. This review will address completed and ongoing trials that have established and continue to clarify the effects of these agents in rectal cancer.

Christopher Jackson, MBChB;Kazimierz Mochlinkski, BSc, MBBS;David Cunningham, MD, FRCP

Neoadjuvant Therapy for Hepatocellular Carcinoma: Is There An Optimal Approach?

The majority of patients who undergo resection for gastric cancer experience relapse and ultimately die of their disease. Therefore, considerable attention has been paid to neoadjuvant and adjuvant strategies to improve surgical outcomes. Two different approaches have been tested in major clinical trials conducted in the past several years: Postoperative chemoradiotherapy was assessed in a US Southwest Oncology Group/Intergroup study (SWOG 9008/INT 0116), and perioperative chemotherapy was studied in a UK Medical Research Council (MRC) randomized trial (the MRC Adjuvant Gastric Infusional Chemotherapy [MAGIC] trial). These trials demonstrated statistically significant survival benefits in patients with resectable gastric cancer. This review will consider these trials and their implications for clinical practice.

Khaldoun Almhanna, MD, MPH;Sujith Kalmadi, MD;Robert Pelley, MD;Richard Kim, MD

PET Finds Responders to Preop Chemotherapy for Esophagogastric Junction Ca

Hepatocellular carcinoma (HCC) is an aggressive tumor that often occurs in the setting of chronic liver disease and cirrhosis. The incidence of hepatocellular carcinoma is increasing in the United States and worldwide. Orthotopic liver transplantation (OLT) is a viable and potentially curative option for selected patients with HCC. Locoregional therapy has been used to control HCC before transplantation because of the limited number of donor organs, to prevent tumor progression, and to decrease the incidence of dropouts from the transplant waiting list. Traditionally, multiple investigational locoregional modalities such as tumor resection, radiofrequency ablation, transarterial chemoembolization, and systemic chemotherapy have been used as "bridging" therapies. While the investigation of novel neoadjuvant treatments is justified in an effort to prevent tumor progression, the absence of randomized controlled trials leaves uncertainty about the utility of these maneuvers in improving outcome. This review summarizes the current data on the different modalities used worldwide in the neoadjuvant treatment of hepatocellular carcinoma, the rationale for these approaches, efficacy, potential complications, and future prospects.

S-1 Plus Cisplatin Demonstrates Significant Improvement in Overall Survival of Advanced Gastric Cancer Patients Over S-1 Alone

Early metabolic imaging with positron emission tomography (PET) identifies responders to neoadjuvant chemotherapy for advanced adenocarcinoma of the esophagogastric junction

Monoclonal Antibodies in Colorectal Cancer: What We Know

Taiho and sanofi-aventis announced the results of a phase III trial in advanced gastric cancer, which shows that the combination of the investigational oral fluoropyrimidine S-1 with cisplatin significantly reduces the risk of death by 22.6% (hazard ratio = 0.774; 95% confidence interval = 0.608-0.985) over S-1 alone.

Jean L. Grem, MD, FACP

Clinical Use of Monoclonal Antibodies to the Epidermal Growth Factor Receptor in Colorectal Cancer

Monoclonal antibodies to the epidermal growth factor receptor (EGFR) are among the promising novel targeted therapies being explored in colorectal cancer. Two such agents that inhibit EGFR signaling by interfering with ligand-binding are cetuximab (Erbitux) and panitumumab (Vectibix). This review will address the use of cetuximab and panitumumab in chemotherapy-refractory colorectal cancer as well as in front-line therapy for the disease, consider predictors of response and resistance, and outline comparisons between these agents.

Barbara Burtness, MD