Colorectal Cancer

Genentech Inc, recently announced that the US Food and Drug Administration (FDA) approved bevacizumab (Avastin) in combination with intravenous fluorouracil (5-FU)-based chemotherapy for second-line metastatic colorectal cancer.

A small molecule that inhibits the insulin-like growth factor 1 receptor (IGF-1R) has blocked the development of human colorectal tumors in mice, according to researchers from OSI Pharmaceuticals, Melville, New York.

An increasing body of evidence suggests that geriatric patients can benefit from and tolerate standard chemotherapy similarly to younger patients in the settings of both early- and advanced-stage colorectal cancer. Assessment of this unique population requires more comprehensive evaluation in addition to routine history, physical examination, and laboratory tests. Specific considerations of their physiologic functional changes will help physicians better manage these patients. Ongoing studies are now designed to better understand the decision-making process, safety profile, and efficacy of various treatment regimens in geriatric patients.

Panitumumab, a new targeted treatment for advanced colorectal cancer, plus best supportive care extended progression-free survival (PFS) significantly, compared with best supportive care alone, Marc Peeters, MD, PhD, of Ghent University Hospital, Belgium, said at the 97th Annual Meeting of the American Association for Cancer Research (AACR) (abstract CP-1). FDA has granted the drug fast-track status, and it could be approved for use by the fall of this year.

A blood-based DNA test to detect colorectal cancer has the potential to increase screening rates and the number of tumors found at an early stage, according to researchers at Epigenomics, Inc. the Seattle-based molecular diagnostics company that is developing the test (see graphic on page 1).

Two large randomized trials have shown that the COX-2 inhibitor celecoxib (Celebrex) significantly reduces the recurrence of colorectal adenomas, according to data presented at the 97th Annual Meeting of the American Association of Cancer Research. However, the trials also found a significantly increased risk of serious cardiovascular (CV) events—strokes and heart attacks—among trial participants taking the drug. Celecoxib researchers and other experts at the meeting emphasized that more needs to be known about how and why celecoxib raises CV risk before it can be recommended for prevention of colorectal cancer.

Carcinoembryonic antigen (CEA) monitoring in patients with stage I-IV colorectal cancer has been, and remains, a controversial issue in oncology practice. Recommendations vary from bimonthly monitoring to no monitoring in the surveillance setting (for stage I-III disease). In the metastatic setting, there are no clear guidelines for CEA follow-up, although continued monitoring in such patients is common in the oncology community. This manuscript reviews the accuracy of CEA testing, its value as a prognostic indicator, and its role in surveillance and response assessment. The limitations of the test in the adjuvant and metastatic settings are illustrated through several case reports from the Colorectal Oncology Clinic at Roswell Park Cancer Institute. Guidelines for CEA monitoring are provided, based on a detailed literature review and institutional experience.

Carcinoembryonic antigen (CEA) monitoring in patients with stage I-IV colorectal cancer has been, and remains, a controversial issue in oncology practice. Recommendations vary from bimonthly monitoring to no monitoring in the surveillance setting (for stage I-III disease). In the metastatic setting, there are no clear guidelines for CEA follow-up, although continued monitoring in such patients is common in the oncology community. This manuscript reviews the accuracy of CEA testing, its value as a prognostic indicator, and its role in surveillance and response assessment. The limitations of the test in the adjuvant and metastatic settings are illustrated through several case reports from the Colorectal Oncology Clinic at Roswell Park Cancer Institute. Guidelines for CEA monitoring are provided, based on a detailed literature review and institutional experience.

Carcinoembryonic antigen (CEA) monitoring in patients with stage I-IV colorectal cancer has been, and remains, a controversial issue in oncology practice. Recommendations vary from bimonthly monitoring to no monitoring in the surveillance setting (for stage I-III disease). In the metastatic setting, there are no clear guidelines for CEA follow-up, although continued monitoring in such patients is common in the oncology community. This manuscript reviews the accuracy of CEA testing, its value as a prognostic indicator, and its role in surveillance and response assessment. The limitations of the test in the adjuvant and metastatic settings are illustrated through several case reports from the Colorectal Oncology Clinic at Roswell Park Cancer Institute. Guidelines for CEA monitoring are provided, based on a detailed literature review and institutional experience.

During the 1980s, the only drug routinely used to treat colorectal carcinoma was single-agent fluorouracil (5-FU), a drug that had shown no proven benefit in the adjuvant setting. Since then, significant improvements in the overall management of colorectal cancer have been made. This review will compare today's standard of care for adjuvant colorectal carcinoma to that practiced 20 years ago. The authors examine key questions asked about adjuvant therapy and the answers that ultimately changed clinical practice standards and improved overall survival for patients diagnosed with this disease. In addition, this review explores whether 5-FU should be given as part of a multidrug regimen and which route of administration is best when this drug is given. Further, the authors delve into both the use of locally directed therapies to the liver or peritoneum to improve outcomes and the selection of patients to receive adjuvant chemotherapy. Finally, a look to the future shows monoclonal antibodies to be an avenue of great promise in fighting colorectal cancer.

Anti-EGFR (epidermal growth factor receptor) therapies, including tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, demonstrate activity in a variety of tumor types. While both inhibit the EGFR pathway, they act via different mechanisms.

Since initial characterization over 40 years ago, strong preclinical and clinical data have clearly established the epidermal growth factor receptor (EGFR) as a worthy molecular target for intervention in cancer therapy. The receptor is expressed, overexpressed, or mutated in many human tumors, including head and neck, colorectal, pancreatic, non-small-cell lung, ovarian, esophageal, gastric, breast, prostate, bladder, and renal cancers. Experiments in several model systems have confirmed that EGFR signaling is involved in regulating several key biologic processes, including cell proliferation, epithelial development, organogenesis, apoptosis, angiogenesis, and differentiation. Furthermore, EGFR function has been shown to be altered and/or dysregulated in a variety of spontaneous tumors.

Overexpression of the epidermal growth factor receptor (EGFR) is correlated with poor prognosis in many human cancers. Two main classes of anticancer agents affect the EGFR: those targeting the extracellular ligand-binding domain and those that block the intracellular tyrosine kinase (TK) domain. Cetuximab (Erbitux) is a mouse/human chimeric monoclonal antibody that targets the ligand-binding domain of the EGFR, whereas erlotinib (Tarceva) and gefitinib (Iressa) are small-molecule TK inhibitors. Common toxicities of agents targeting the EGFR differ from those associated with traditional chemotherapy. Given the common pathway through which these agents work, some adverse events are similar. Many patients treated with these agents develop an acne-like rash on the face and upper body, most likely related to keratinocyte alterations and hair follicle proliferation and maturation. Although clinical manifestation of this reaction closely resembles acne vulgaris, the histology is more similar to infectious folliculitis. Other adverse events appear to be related to a drug class or individual agent. For example, interstitial lung disease is a rare but potentially fatal reaction that has been reported with gefitinib. Hypomagnesemia reported in association with cetuximab may be related to EGFR blockade in the kidney. Anaphylactic or anaphylactoid infusion reactions are also seen with cetuximab, as with other monoclonal antibodies.

Colon cancer remains one of the most common human malignancies, with an annual global incidence of slightly less than 1 million patients per year.

During the 1980s, the only drug routinely used to treat colorectal carcinoma was single-agent fluorouracil (5-FU), a drug that had shown no proven benefit in the adjuvant setting. Since then, significant improvements in the overall management of colorectal cancer have been made. This review will compare today's standard of care for adjuvant colorectal carcinoma to that practiced 20 years ago. The authors examine key questions asked about adjuvant therapy and the answers that ultimately changed clinical practice standards and improved overall survival for patients diagnosed with this disease. In addition, this review explores whether 5-FU should be given as part of a multidrug regimen and which route of administration is best when this drug is given. Further, the authors delve into both the use of locally directed therapies to the liver or peritoneum to improve outcomes and the selection of patients to receive adjuvant chemotherapy. Finally, a look to the future shows monoclonal antibodies to be an avenue of great promise in fighting colorectal cancer.

Surveillance screening for colon and breast cancer appears to diminish 5 years after the original diagnosis.

Age alone should not be a contraindication to FOLFOX4 chemotherapy in older adults with colorectal cancer.

NeoGuide Systems, Inc.'s computer-assisted colonoscopy system has received FDA 501(k) marketing clearance. The company's NeoGuide Endoscopy System is designed to eliminate the "looping" that may occur when the advancing endoscope displaces the colon and stretches the surrounding tissue.

The first comprehensive assessment of cancer care quality in the United States indicates adherence to recommended care for patients with breast or colorectal cancer is excellent overall, but specific areas need improvement. Overall, breast cancer patients received 86% of generally recommended care, based on 36 quality-care measures. Patients with colorectal cancer received 78% of generally recommended care, based on 25 quality-care measures.

March 2006 marks the seventh annual National Colorectal Cancer Awareness Month. The national nonprofit Cancer Research and Prevention Foundation (CRPF) and its partners have activities planned to increase general knowledge in the United States about colorectal cancer, to advocate screening, and to encourage potentially life-saving lifestyle changes.

Compared with FOLFIRI, the FOLFOXIRI regimen increases the rate of radical resection, prolongs time to progression, and may improve survival when used as first-line therapy for metastatic colorectal cancer, new data show. Alfredo Falcone, MD, professor of medical oncology, University of Pisa, and chairman of Oncology, Livorno Hospital, presented the findings at the 2006 Gastrointestinal Cancers Symposium (abstract 227).

Approximately 6% of colorectal cancers can be attributed to recognizable heritable germline mutations. Familial adenomatous polyposis is an autosomal dominant syndrome classically presenting with hundreds to thousands of adenomatous colorectal polyps that are caused by mutations in the APC gene.

Approximately 6% of colorectal cancers can be attributed to recognizable heritable germline mutations. Familial adenomatous polyposis is an autosomal dominant syndrome classically presenting with hundreds to thousands of adenomatous colorectal polyps that are caused by mutations in the APC gene.

Approximately 6% of colorectal cancers can be attributed to recognizable heritable germline mutations. Familial adenomatous polyposis is an autosomal dominant syndrome classically presenting with hundreds to thousands of adenomatous colorectal polyps that are caused by mutations in the APC gene.

Colon cancer is a major public health problem. The primary treatment is resection. For patients with early-stage disease, surgery results in excellent survival rates. In contrast, patients with locally advanced tumors arising in "anatomically immobile" segments of large bowel have a less satisfactory outcome, in part secondary to compromised surgical clearance. Patterns-of-failure analyses suggest that for tumors that invade adjacent organs, exhibit perforation or fistula, or are subtotally resected, local failure rates exceed 30%. Multiple single-institution retrospective studies have shown improved local control and possibly survival with the addition of external irradiation and/or intraoperative radiation. In contrast, a recent Intergroup trial failed to show any benefit by the addition of adjuvant radiation therapy combined with chemotherapy. Interpretation of this trial's results is handicapped by low patient accrual. With the advent of novel and more effective systemic therapies for metastatic colon cancer, current and future clinical research will address the efficacy of these agents in the adjuvant setting. Adjuvant radiation therapy should be considered in patients with colon cancer at high risk for local failure.

Practice standards call for colonoscopy for all patients who have positive guaiac fecal occult blood test (FOBT) screening for colorectal cancer. A new study suggests that using a confirmatory immunochemical FOBT in patients who are only weakly or moderately positive on guaiac FOBT would eliminate many false positives and reduce the need for colonoscopy without jeopardizing outcomes.

Colon cancer is a major public health problem. The primary treatment is resection. For patients with early-stage disease, surgery results in excellent survival rates. In contrast, patients with locally advanced tumors arising in "anatomically immobile" segments of large bowel have a less satisfactory outcome, in part secondary to compromised surgical clearance. Patterns-of-failure analyses suggest that for tumors that invade adjacent organs, exhibit perforation or fistula, or are subtotally resected, local failure rates exceed 30%. Multiple single-institution retrospective studies have shown improved local control and possibly survival with the addition of external irradiation and/or intraoperative radiation. In contrast, a recent Intergroup trial failed to show any benefit by the addition of adjuvant radiation therapy combined with chemotherapy. Interpretation of this trial's results is handicapped by low patient accrual. With the advent of novel and more effective systemic therapies for metastatic colon cancer, current and future clinical research will address the efficacy of these agents in the adjuvant setting. Adjuvant radiation therapy should be considered in patients with colon cancer at high risk for local failure.

DENVER-Giving chemotherapy concurrently with radiation therapy before surgery for T3-T4 rectal cancer improves the rate of local control, investigators reported at the 47th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (abstract 4).

In the past several years, the impact of the new biologic therapies oncolorectal cancer has been dramatic. The focus of this article is to summarizesome of the key advances of incorporating biologically targetedtherapies into the routine management of patients with colorectal cancer.We will review important data presented at the 2005 American Society ofClinical Oncology annual meeting and discuss the incorporation of thesedata into the most optimal management of our patients, including howbest to manage side effects and keep quality of life as high as possible.

Several developments in the past few years have incrementally progressedthe field and provided additional insights into the managementof advanced colorectal cancer. This review discusses the componentsof current cytotoxic chemotherapy regimens for advanced colorectalcancer: fluorouracil (5-FU), capecitabine (Xeloda), irinotecan(Camptosar), and oxaliplatin (Eloxatin). The equivalence of severalfront-line regimens has provided opportunities for increased tailoringof therapies for individual patients. Preliminary data onpharmacogenomics provides hope that we will be able to better matchpatients with regimens and doses on the basis of individualized predictionsof toxicity and response. The importance of second-line therapyin overall survival has again been highlighted; the best outcomes haveoccurred in patients treated with 5-FU, oxaliplatin, and irinotecan incombination with targeted therapies during the course of their disease.Elderly patients are no exception to this finding. Combination regimensand second-line therapy should be offered to elderly patients whohave adequate performance status and no contraindicated comorbidconditions, without regard for their chronological age.