Gastrointestinal Cancer

Over the past decade, new cytotoxic and biologic therapies beyond the old standard-of-care, biomodulated fluorouracil (5-FU), have become available for the treatment of metastatic colorectal cancer (mCRC). The introductions of irinotecan (Camptosar), oxaliplatin (Eloxatin), and bevacizumab (Avastin) have prolonged survival, but the optimal use of these new therapies remains to be determined. Issues remain regarding management of toxicities, treatment of elderly patients or those with poor performance status, and the duration of treatment with front-line therapy. This article reviews recent and ongoing studies of newer therapies in an effort to determine the best use of these drugs in the treatment of mCRC. Current data support the front-line use of bevacizumab added to either 5-FU/leucovorin alone or 5-FU/leucovorin in combination with oxaliplatin (FOLFOX/bevacizumab) or irinotecan (FOLFIRI/bevacizumab). If oxaliplatin is used in first-line therapy, oxaliplatin should be discontinued before the development of severe neurotoxicity and be reintroduced or replaced with irinotecan on disease progression. Definitive conclusions on the sequence and duration of front-line therapy and the most effective strategy to ameliorate toxicity await results of ongoing prospective clinical trials.

Over the past decade, new cytotoxic and biologic therapies beyond the old standard-of-care, biomodulated fluorouracil (5-FU), have become available for the treatment of metastatic colorectal cancer (mCRC). The introductions of irinotecan (Camptosar), oxaliplatin (Eloxatin), and bevacizumab (Avastin) have prolonged survival, but the optimal use of these new therapies remains to be determined. Issues remain regarding management of toxicities, treatment of elderly patients or those with poor performance status, and the duration of treatment with front-line therapy. This article reviews recent and ongoing studies of newer therapies in an effort to determine the best use of these drugs in the treatment of mCRC. Current data support the front-line use of bevacizumab added to either 5-FU/leucovorin alone or 5-FU/leucovorin in combination with oxaliplatin (FOLFOX/bevacizumab) or irinotecan (FOLFIRI/bevacizumab). If oxaliplatin is used in first-line therapy, oxaliplatin should be discontinued before the development of severe neurotoxicity and be reintroduced or replaced with irinotecan on disease progression. Definitive conclusions on the sequence and duration of front-line therapy and the most effective strategy to ameliorate toxicity await results of ongoing prospective clinical trials.

Over the past decade, new cytotoxic and biologic therapies beyond the old standard-of-care, biomodulated fluorouracil (5-FU), have become available for the treatment of metastatic colorectal cancer (mCRC). The introductions of irinotecan (Camptosar), oxaliplatin (Eloxatin), and bevacizumab (Avastin) have prolonged survival, but the optimal use of these new therapies remains to be determined. Issues remain regarding management of toxicities, treatment of elderly patients or those with poor performance status, and the duration of treatment with front-line therapy. This article reviews recent and ongoing studies of newer therapies in an effort to determine the best use of these drugs in the treatment of mCRC. Current data support the front-line use of bevacizumab added to either 5-FU/leucovorin alone or 5-FU/leucovorin in combination with oxaliplatin (FOLFOX/bevacizumab) or irinotecan (FOLFIRI/bevacizumab). If oxaliplatin is used in first-line therapy, oxaliplatin should be discontinued before the development of severe neurotoxicity and be reintroduced or replaced with irinotecan on disease progression. Definitive conclusions on the sequence and duration of front-line therapy and the most effective strategy to ameliorate toxicity await results of ongoing prospective clinical trials.

Esophageal, gastroesophageal junction, and gastric cancers are underpublicized but are frequently lethal, and gastroesophageal junction adenocarcinomas are increasingly common diseases in the United States and around the world. Although often grouped together in studies of chemotherapy, clear distinctions can be made in the locoregional therapy of these diseases. Esophageal squamous cell carcinomas may be treated with surgery or radiation with concurrent chemotherapy, whereas esophageal adenocarcinomas and gastroesophageal junction adenocarcinomas are often treated with all three treatment modalities. Over the past several years, it has become increasingly evident that gastric cancer is a disease that is potentially sensitive to chemotherapy. In the perioperative setting—at least in the Western world—chemotherapy and sometimes radiation are applied. However, the optimal chemotherapy for advanced gastric or esophageal cancer remains unsettled, and there is no single standard regimen. Several new chemotherapy agents have demonstrated activity in these diseases, but the best chemotherapy remains to be determined. This paper will review the role of chemotherapy in gastroesophageal cancers.

Curcumin, an ingredient in the dietary spice turmeric (see box), may be useful in treating pancreatic cancer, according to two groups of investigators who presented their work at the Society for Integrative Oncology Third International Conference.

In patients with colorectal cancer, a 'hand-in' approach to laparoscopic surgery—hand-assisted laparoscopic surgery (HALS)—may yield benefits beyond those of traditional laparoscopic techniques, particularly reduced operation time.

Researchers have developed a two-gene test that can accurately distinguish between two common forms of gastrointestinal cancers.

The Jay Monahan Center for Gastrointestinal Health at New York-Presbyterian Hospital/Weill Cornell Medical Center is teaming up with New York City's taxi drivers to remind New Yorkers and visitors to the city to get screened for colon cancer.

Nexavar Effective in Advanced HCC: Phase III Trial Stopped

About 6% of colorectal cancers are caused by genetic mutations associated with hereditary colorectal cancer syndromes. The most common hereditary cancer syndromes nurses are likely to encounter include hereditary nonpolyposis colon cancer or Lynch syndrome, familial adenomatous polyposis, attenuated familial adenomatous polyposis, and MYH polyposis. Current colorectal cancer recommendations for risk management, screening, and surveillance are complex and based on level of colorectal cancer risk and whether an individual carries a genetic mutation associated with a hereditary colorectal cancer syndrome. Caring for patients with hereditary colorectal cancer syndromes requires nurses to understand how to identify individuals and families at risk for hereditary colorectal cancer, refer to appropriate resources, and provide accurate information regarding screening, surveillance, and management. Nurses play a critical role in assessing colorectal cancer risk, obtaining an accurate family history of cancer, and providing information concerning appropriate cancer screening and surveillance.

About 6% of colorectal cancers are caused by genetic mutations associated with hereditary colorectal cancer syndromes. The most common hereditary cancer syndromes nurses are likely to encounter include hereditary nonpolyposis colon cancer or Lynch syndrome, familial adenomatous polyposis, attenuated familial adenomatous polyposis, and MYH polyposis. Current colorectal cancer recommendations for risk management, screening, and surveillance are complex and based on level of colorectal cancer risk and whether an individual carries a genetic mutation associated with a hereditary colorectal cancer syndrome. Caring for patients with hereditary colorectal cancer syndromes requires nurses to understand how to identify individuals and families at risk for hereditary colorectal cancer, refer to appropriate resources, and provide accurate information regarding screening, surveillance, and management. Nurses play a critical role in assessing colorectal cancer risk, obtaining an accurate family history of cancer, and providing information concerning appropriate cancer screening and surveillance.

In patients with stage II/III stomach cancer, postsurgical administration of S-1, an experimental chemotherapy agent, improves overall survival, compared with surgery alone

This 72-year-old woman undergoes surveillance colonoscopy. She has a history of small colonic adenomas removed from the distal colon and of a sessile hyperplastic polyp in the cecum. Prior biopsies have demonstrated only hyperplastic changes and no evidence of adenomatous or dysplastic features. Her last colonoscopic examination was more than 3 years ago.

Cell Genesys, Inc, announced follow-up data from a phase II clinical trial of GVAX immunotherapy for pancreatic cancer in 60 patients with operable pancreatic cancer who received the immunotherapy after surgical resection of their tumor and adjuvant radiation and chemotherapy.

ImClone Systems and Bristol-Myers Squibb have announced that a phase III study of cetuximab (Erbitux) plus FOLFIRI (an irinotecan-based chemotherapy regimen) met the primary endpoint of increasing median duration of progression-free survival (PFS) over FOLFIRI alone in patients with previously untreated metastatic colorectal cancer.

British researchers have developed a vaccine that stimulates colorectal cancer patients' immune systems to fight cancerous cells. In a clinical trial of 67 patients, investigators at the University of Nottingham observed that when the vaccines were administered before and after surgery to remove cancerous tumors, they helped stimulated immune cell production in up to 70% of patients. These results were published in a recent issue of Clinical Cancer Research.

The three papers contained in this supplement to ONCOLOGY were designed to serve as practical "keep on the shelf" references for the current management of metastatic colon cancer and screening and management of patients at high risk of colon cancer.

Traditional therapeutic concepts and treatment regimens for colorectal cancer are currently changing with the demonstration of the efficacy of biologic agents in this disease setting. The addition of the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab (Avastin) to conventional chemotherapy in the first- and second-line settings has shown a survival benefit; this outcome has helped to rapidly change the standard of care. Other targeted agents, such as anti-epidermal growth factor receptor (EGFR) antibodies, have shown proof of efficacy in colorectal cancer as well. The molecular targeted therapies are associated with toxicity profiles that are distinctly different from those seen with conventional chemotherapy. A notable difference is the absence of high risk for myelosuppression, diarrhea, or alopecia, which are common side effects of cytotoxic chemotherapy. This article will explore the toxicities associated with targeted therapies in detail in an attempt to provide assistance to the practicing oncologist in detecting and managing these side effects in their patients. In particular, the article will focus on the side effects associated with the three currently approved targeted drugs: the anti-VEGF monoclonal antibody bevacizumab and the anti-EGFR monoclonal antibodies cetuximab (Erbitux) and panitumumab (Vectibix).

Clinicians need to develop treatment strategies for subpopulations of patients with colorectal cancer, according to Richard Goldberg, MD, professor of medicine and division chief of hematology-oncology, University of North Carolina School of Medicine, Chapel Hill. He spoke at the 2006 Gastrointestinal Oncology Conference, sponsored by the International Society of Gastrointestinal Oncology.

In clinical trials of panitumumab (Vectibix), 8% to 13% of patients with refractory colorectal cancer achieved a partial tumor response with the drug, according to data from five studies reviewed at the 2006 Gastrointestinal Oncology Conference. The meeting was sponsored by the International Society of Gastrointestinal Oncology.

Industry and government need to form a new alliance to more efficiently conduct clinical trials, Howard Hochster, MD, professor of medicine, New York University Medical Center, said at the 2006 Gastrointestinal Oncology Conference, sponsored by the International Society of Gastrointestinal Oncology.

Two of the hottest targets in colorectal cancer are spurring "lots of enthusiasm," Lee M. Ellis, MD, professor of surgical oncology and cancer biology, The University of Texas M.D. Anderson Cancer Center, said at the 2006 Gastrointestinal Oncology Conference, sponsored by the International Society of Gastrointestinal Oncology. The two targets, c-Src and urokinase plasminogen activator receptor (uPAR), both play key roles in tumor metastases and migration.

In a phase I study, the chimeric monoclonal antibody, RAV12 (Raven biotechnologies inc) has shown preliminary evidence of efficacy in gastrointestinal (GI) tumors. Howard A Burris III, MD, director of drug development at the Sarah Cannon Cancer Center, Nashville, one of three centers where the trial is underway, spoke about the research at the Chemotherapy Foundation Symposium XXIV

Roche announced that a large, international phase III study (NO16966) enrolling 2,035 previously untreated metastatic colorectal cancer patients met both of its primary endpoints.

Colorectal cancer is the second most common cause of cancer death in the United States. It is estimated that about 55,000 patients will die this year due to advanced colorectal cancer. These grim statistics persist despite a marked increase in the rate of screening colonoscopies and improvements in adjuvant chemotherapy. Successful chemoprevention strategies may reduce the risk of new colorectal cancers, thus decreasing related overall morbidity and mortality.

Sunitinib malate (Sutent)is an effective treatment option forpatients with gastrointestinal stromal tumor(GIST) after imatinib mesylate(Gleevec) therapy has failed, accordingto a multicenter, randomized, placebocontrolledphase III clinical trial.

Gleevec (imatinib mesylate) tablets has receivedFDA approval to treat patients with fiverare, potentially life-threatening disorders,representing the first time that aregulatory authority has ever simultaneouslyapproved one targeted medicinefor so many disorders, according toNovartis, maker of Gleevec.

A phase III trial has shown that XELOX is as effective as FOLFOX4 in patients with metastatic colorectal cancer, and that adding the targeted agent bevacizumab (Avastin) to either regimen improves progressionfree survival (PFS).

The science supporting molecularly targeted therapies for the treatment of patients with solid tumors continues to evolve. Nurses are challenged to understand cell signaling, molecular targeting, and the mechanism of action of targeted agents. Two cell signal transduction pathways regulate the development, proliferation, and metastasis of solid tumors: the human epidermal growth factor (HER) receptor pathway and the vascular endothelial growth factor (VEGF) receptor pathway. Several novel pharmacologic agents with distinct indications and methods of administration target the HER and VEGF molecular pathways.

Following priority review, the US Food and Drug Administration (FDA) has approved Amgen Inc's panitumumab (Vectibix) for the treatment of advanced colon cancer.