Colorectal Cancer

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.

Colorectal cancer is a worldwide public health problem, with nearly 800,000new cases diagnosed each year resulting in approximately 500,000deaths. In the United States, it is the second leading cause of cancer mortality,and nearly 60,000 deaths will be attributed to this disease in 2005. Whendiagnosed as advanced, metastatic disease, colorectal cancer is traditionally associatedwith a poor prognosis, with 5-year survival rates in the range of 5% to 8%. Thissurvival rate has remained unchanged over the past 35 to 40 years. However, duringthe past 5 years, significant advances have been made in treatment options so thatimprovements in 2-year survival are now being reported, with median survival ratesin the 21- to 24-month range in patients with metastatic disease.

Continuing advances in immunology and molecular biology duringthe past several decades have provided optimism that immunomodulatorystrategies may be clinically useful in patients with cancer.Key advances have included: (1) recognition of the critical role of theantigen-presenting cell and greatly improved understanding of antigenprocessing and presentation, including the molecular interactionsbetween HLA molecules and antigenic epitopes on the antigen-processingcell and the receptors on T cells, and (2) the roles ofcostimulatory molecules such as B7.1, ICAM-1, and LFA-3 in the inductionand maintenance of an immune response. In addition, newtechniques have allowed us to identify immunogenic antigenic determinants,alter their binding affinities, and evaluate the overall successof the intervention through both in vivo and in vitro assays.Carcinoembryonic antigen (CEA) is overexpressed in a large numberof gastrointestinal, lung, and breast cancers. Clinical trials have establishedtreatment protocols using viral vectors to immunize patients toCEA without producing deleterious autoimmune phenomena. By combiningvarious vectors to include MUC-1 and/or CEA plus costimulatorymolecules in a prime-and-boost regimen, we are beginning to see signsthat this intervention can not only produce changes in immune functionbut also potentially improve clinical outcomes. Phase III studies totest these hypotheses are under way.

ORLANDO-Sentinel lymph node mapping (SLNM) upstaged nodal metastases in 15% of colon cancer patients in a single-institution retrospective study of more than 300 colon cancer patients at stages T1 to T4. Routine pathological examination after conventional surgery understages 15% to 20% of colorectal cancer patients, the researchers said. Thus, SLNM has a potential survival benefit: "Higher numbers of patients with nodal metastases in the group that underwent SLNM went on to receive chemotherapy," they reported. "This may explain the reduced recurrence rates seen in these patients, which may lead to prolonged survival."

ORLANDO-Adding high-dose bevacizumab (Avastin) to FOLFOX4 improves overall survival, progression-free survival (PFS), and response in previously treated patients who have advanced colorectal cancer, Bruce J. Giantonio, MD, reported at the 41st Annual Meeting of the American Society of Clinical Oncology (abstract 2). Dr. Giantonio, of the University of Pennsylvania, presented results of the Eastern Cooperative Oncology Group (ECOG) E3200 study.

Despite enormous advances in the treatment of colorectal cancer,there is no single standard treatment approach for all patients. However,there are general principles of management that can be used toguide therapy. The clinician who fails to individualize therapy forcolorectal cancer is likely not taking full advantage of all therapeuticoptions available. Reviewing key clinical evidence that can help informdecision-making, this article addresses important questions in colorectalcancer management, including: Should bevacizumab (Avastin) be acomponent of most patients’ first-line treatment? Is there a role forcontinuing bevacizumab in subsequent regimens? Is there a role forcetuximab (Erbitux) in standard first-line chemotherapy? Are therepractices in colorectal cancer that have become widely accepted withoutdirect supportive data?

OTTAWA, CANADA-Forolder and less fit cancer patients, whoare more likely to experience greatertoxicity but less benefit from combinationchemotherapy, a more reason

PARIS, FRANCE-Analysisof disease-free survival data at 4 yearsinto the MOSAIC trial “amplifies thebenefit of FOLFOX4 obtained at 3

NAPLES, ITALY-As firstlinetherapy in elderly patients withmetastatic colorectal cancer, XELOX(capecitabine [Xeloda] and oxaliplatin(Eloxatin]) achieved an objectivetumor response rate of 41% (abstract

ORLANDO-XELOX (capecitabine[Xeloda] and oxaliplatin [Eloxatin])is effective and well tolerated asfirst-line treatment for elderly patients

BOLOGNA, ITALY-Preliminaryresults of a small phase II advancedcolorectal cancer trial comparinga protracted fluorouracil

HOUSTON-Concomitantboost radiotherapy plus capecitabine(Xeloda) produces pathologic responserates comparable to those of

VILLEJUIF, FRANCE-In thefirst randomized comparison of aschedule of FOLFOX6 (fluorouracil[5-FU], leucovorin, oxaliplatin [Eloxatin])vs standard XELOX (capecitab