Gastrointestinal Cancer

blood-based marker called colon cancer–specific antigen-2 (CCSA-2) may be an accurate indicator of colorectal cancer

Gastrointestinal stromal tumors have until recently had a uniformly poor prognosis with lack of effective drug therapies. These tumors usually have activating mutations in either KIT or PDGFR-α tyrosine kinase receptors. Over the past decade, imatinib (Gleevec), a selective tyrosine kinase inhibitor has become the standard of care for the first-line treatment of patients with unresectable and metastatic disease. For patients with imatinib-resistant disease or intolerant to the side effects of imatinib, sunitinib (Sutent), a multitargeted tyrosine kinase inhibitor was recently approved. For earlier-stage disease, status post–complete surgical excision, preliminary data seem encouraging for the role of adjuvant imatinib in prolonging patients' disease-free interval. The impact of neoadjuvant drug therapy needs to be further classified and explored. With additional evaluation of other tyrosine kinase inhibitors and novel therapies against other molecular markers, the treatment paradigm for this malignancy should continue to evolve.

Complete evaluation of the lymph node basin after surgical resection for colon cancer is important for the accurate identification of nodal involvement and for the complete resection of disease.

Data published in the New England Journal of Medicine show that oral capecitabine (Xeloda) and oxaliplatin (Eloxatin) in combination with epirubicin (Ellence) is a comparable alternative to infused fluorouracil (5-FU) and cisplatin with epirubicin in patients with previously untreated, advanced esophagogastric cancer.

Sunitinib malate (Sutent, SU011248) is an oral multitargeted tyrosine kinase inhibitor used for treatment of renal cell carcinoma and gastrointestinal stromal tumor. We report a case of a patient who developed Guillain-Barré syndrome after initial treatment with sunitinib, with recurrent symptoms upon reintroducing the drug. This is the first report of such an effect. The literature on chemotherapy-induced Guillain-Barré syndrome is also reviewed. Oncology providers should be aware of this rare but potentially serious possible adverse effect of sunitinib.

Sunitinib malate (Sutent, SU011248) is an oral multitargeted tyrosine kinase inhibitor used for treatment of renal cell carcinoma and gastrointestinal stromal tumor. We report a case of a patient who developed Guillain-Barré syndrome after initial treatment with sunitinib, with recurrent symptoms upon reintroducing the drug. This is the first report of such an effect. The literature on chemotherapy-induced Guillain-Barré syndrome is also reviewed. Oncology providers should be aware of this rare but potentially serious possible adverse effect of sunitinib.

multicenter, open-label, randomized phase III trial recently published in the New England Journal of Medicine (357:2040-2048, 2007) demonstrated that cetuximab (Erbitux) as a single agent significantly improved overall survival in patients with metastatic colorectal cancer (mCRC) refractory to approved chemotherapy agents.

Erlotinib (Tarceva) is a human epidermal growth factor receptor type 1/epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor initially approved by the US Food and Drug Administration for the treatment of patients with locally advanced or metastatic non–small-cell lung cancer after failure of at least one prior chemotherapy regimen. In this report, we present the pivotal study that led to the approval of erlotinib in combination with gemcitabine (Gemzar) in patients with locally advanced/metastatic chemonaive pancreatic cancer patients. The combination demonstrated a statistically significant increase in overall survival accompanied by an increase in toxicity. Physicians and patients now have a new option for the treatment of locally advanced/metastatic adenocarcinoma of the pancreas.

Erlotinib (Tarceva) is a human epidermal growth factor receptor type 1/epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor initially approved by the US Food and Drug Administration for the treatment of patients with locally advanced or metastatic non–small-cell lung cancer after failure of at least one prior chemotherapy regimen. In this report, we present the pivotal study that led to the approval of erlotinib in combination with gemcitabine (Gemzar) in patients with locally advanced/metastatic chemonaive pancreatic cancer patients. The combination demonstrated a statistically significant increase in overall survival accompanied by an increase in toxicity. Physicians and patients now have a new option for the treatment of locally advanced/metastatic adenocarcinoma of the pancreas.

US Food and Drug Administration (FDA) has granted an expanded clearance for the CellSearch System to be used as an aid in the monitoring of metastatic colorectal cancer

Inoperable pancreatic adenocarcinoma is a dilemma that oncologists frequently encounter. Only 15% to 20% of patients are diagnosed when cancer of the pancreas is still surgically resectable. However, pancreaticoduodenectomy is the only curative option for this disease and should be offered to all patients who meet resection criteria and do not have significant comorbidities. For inoperable pancreatic cancer, the goals of treatment are to palliate symptoms and prolong life. Improved survival in locally advanced disease has been demonstrated with chemoradiation plus fluorouracil or with gemcitabine (Gemzar) alone. In metastatic disease, single-agent gemcitabine has been associated with improvement in symptoms and survival. Trials combining various chemotherapeutic agents with gemcitabine have not had a significant impact on overall survival, although meta-analyses suggest a small benefit. The targeted agent erlotinib (Tarceva) has shown a modest improvement in overall survival in combination with gemcitabine. This combination is another option for first-line therapy in patients with locally advanced or metastatic disease. Despite these recent advances, survival for patients with inoperable pancreatic cancer continues to be poor. Future investigations need to focus on understanding the molecular nature of this malignancy, with the goal of developing interventions based on this knowledge.

Inoperable pancreatic adenocarcinoma is a dilemma that oncologists frequently encounter. Only 15% to 20% of patients are diagnosed when cancer of the pancreas is still surgically resectable. However, pancreaticoduodenectomy is the only curative option for this disease and should be offered to all patients who meet resection criteria and do not have significant comorbidities. For inoperable pancreatic cancer, the goals of treatment are to palliate symptoms and prolong life. Improved survival in locally advanced disease has been demonstrated with chemoradiation plus fluorouracil or with gemcitabine (Gemzar) alone. In metastatic disease, single-agent gemcitabine has been associated with improvement in symptoms and survival. Trials combining various chemotherapeutic agents with gemcitabine have not had a significant impact on overall survival, although meta-analyses suggest a small benefit. The targeted agent erlotinib (Tarceva) has shown a modest improvement in overall survival in combination with gemcitabine. This combination is another option for first-line therapy in patients with locally advanced or metastatic disease. Despite these recent advances, survival for patients with inoperable pancreatic cancer continues to be poor. Future investigations need to focus on understanding the molecular nature of this malignancy, with the goal of developing interventions based on this knowledge.

Inoperable pancreatic adenocarcinoma is a dilemma that oncologists frequently encounter. Only 15% to 20% of patients are diagnosed when cancer of the pancreas is still surgically resectable. However, pancreaticoduodenectomy is the only curative option for this disease and should be offered to all patients who meet resection criteria and do not have significant comorbidities. For inoperable pancreatic cancer, the goals of treatment are to palliate symptoms and prolong life. Improved survival in locally advanced disease has been demonstrated with chemoradiation plus fluorouracil or with gemcitabine (Gemzar) alone. In metastatic disease, single-agent gemcitabine has been associated with improvement in symptoms and survival. Trials combining various chemotherapeutic agents with gemcitabine have not had a significant impact on overall survival, although meta-analyses suggest a small benefit. The targeted agent erlotinib (Tarceva) has shown a modest improvement in overall survival in combination with gemcitabine. This combination is another option for first-line therapy in patients with locally advanced or metastatic disease. Despite these recent advances, survival for patients with inoperable pancreatic cancer continues to be poor. Future investigations need to focus on understanding the molecular nature of this malignancy, with the goal of developing interventions based on this knowledge.

Bayer HealthCare and Onyx Pharmaceuticals (Emeryville, California) have halted the phase III Asia-Pacific liver cancer study after a planned review by an independent data monitoring committee found that sorafenib (Nexavar) tablets significantly improved overall survival, progression-free survival, and time to progression in patients with advanced hepatocellular carcinoma

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

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,"

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.

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.

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

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

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

Avalon initiates phase II trial of AVN944 in pancreatic cancer

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

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.

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.

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.

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.

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.

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.

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.