Colorectal Cancer

In a move more than 2 years in the making, a National Quality Forum (NQF) recently endorsed the first nationally recognized hospital-based performance measures for quality of care for breast and colorectal 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.

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.

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.

A new way to select for further testing those people who are at risk for Lynch syndrome may increase detection of the disorder, also known as hereditary nonpolyposis colorectal cancer (HNPCC). The syndrome, which predisposes people to developing colorectal cancer at a young age, is caused by germline mutations in DNA mismatch repair (MMR) genes.

Better communication is needed between oncologists and their patients regarding the benefits and risks of adjuvant therapy

Preliminary findings from Italian researchers show that adding oxaliplatin (Eloxatin) to preoperative chemoradiotherapy (CRT) for rectal cancer is feasible and safe, and does not adversely affect the ability to carry out subsequent surgery.

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.

The monoclonal antibody bevacizumab (Avastin) is likely to have a variety of uses in cancer treatment but also carries with it risks that require careful monitoring by oncology nursing staff

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.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in United States. For nearly 50 years, fluorouracil has been the only anticancer drug proven to benefit patients with metastatic CRC (mCRC), and it continues to be the backbone on which most treatment regimens are built. In the past 10 years, development of the topoisomerase I inhibitor irinotecan (Camptosar), the third-generation platinum analog oxaliplatin (Eloxatin), and the oral fluoropyrimidine capecitabine (Xeloda) advanced mCRC treatment and opened up an era of combination chemotherapy. More recently, monoclonal antibodies such as bevacizumab (Avastin), cetuximab (Erbitux), and panitumumab (Vectibix) have become available for use in mCRC treatment in combination with cytotoxic agents and as monotherapies. The addition of these targeted agents to the mCRC treatment armamentarium has resulted in more therapeutic options and improved treatment outcomes for the patients. The prospect of mCRC treatment is ever promising as more targeted agents such as vatalanib are being introduced and as intelligent combination regimens are being designed based upon a better understanding of pharmacokinetics. In this article we review various treatment options, including cytotoxic and targeted agents, currently available for patients with mCRC.

Advances in molecular genetics have evolved at such a fast pace that physicians may be bewildered about their clinical translation into patient care. However, genetic counselors, particularly those trained in cancer genetics, have been extremely helpful. The challenge to the physician, however, calls for an understanding of the natural history of hereditary cancer syndromes, which is often reflected in the pedigree. Pedigree/family history information must be compiled in sufficient detail to arrive at the most likely hereditary cancer syndrome diagnosis so that the molecular geneticist can search for the mutation. Finally, the challenge to the clinician is melding this into an accurate diagnosis, in order to provide highly targeted screening and management for high-risk patients. This article is an attempt to crystallize all of these issues in a format that will help physicians—particularly those in the oncology community—to meet this challenge effectively.

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).

Results from Oncolytics Biotech's phase I trial of Reolysin, its oncolytic reovirus, show stable disease in 7 of 32 patients with advanced or metastatic solid tumors refractory to standard therapy or for which no curative standard therapy exists. Dr. Timothy Yap of The Institute of Cancer Research, Sutton, UK, presented the study at the 18th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics

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.

A study published in the December issue of Gastroenterology has shown that medium-sized polyps found in the colon with flexible sigmoidoscopy and subsequently evaluated by full colonoscopy are associated with a significant number of advanced adenomas and cancers.

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.

An innovative cancer agent called PHA-739358, which inhibits one of the aurora proteins, has shown indications of potential benefit in 7 of 36 patients (19.4%) with advanced or metastatic solid tumors who participated in a phase I dosing and toxicity study, Dutch researchers reported at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics

Sirtex is supporting a phase I trial of its SIR-Sphere microspheres as first-line therapy of liver metastases in patients with colorectal cancer in combination with chemotherapy (the FOLFOX-6 and FOLFIRI regimens). The principal investigator is Seza Gulec, MD, director of the Goshen Cancer Institute's Hepatic Oncology Program in Goshen, Indiana, where the trial is being conducted.

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.

Adding the targeted antibody cetuximab (Erbitux) to standard cytotoxic chemotherapy as first-line treatment for patients with advanced colorectal cancer improves response rates, two groups of researchers said at the 31st Congress of the European Society for Medical Oncology (ESMO).

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.