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New Treatments for Colorectal Cancer

Traditional chemotherapy is somewhat a hit-or-miss affair. Chemotherapeutic drugs attack all fast-growing cells, both healthy and cancerous. The new, targeted, therapies promise to spare healthy cells and to concentrate effort on the cancer.

People sometimes talk of a "magic bullet" that can be introduced into the body to cure cancer. This is unlikely, because cancer has many forms, and no one treatment is suitable for all cancers. However, with the advent of targeted therapy, customized treatment is one step closer to a cure and each new advance is making the reality of turning colorectal cancer into a chronic disease.

Monoclonal antibodies and other targeted therapies

The following information was provided by Jean Maroun, MD, a member of CCAC’s Medical Advisory Board

Nearly two decades ago the science world was abuzz about the potential of monoclonal antibodies. We have had to wait some time for the potential to be realized, but it is here now in the form of cetuximab and similar drugs.

Natural antibodies are a type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can recognize and bind to only one specific antigen, and this binding allows the antibody to interfere with the life-cycle of the antigen. Monoclonal antibodies are manufactured. They are derived from a single (mono) cell or its identical progeny (clones) and, like naturally-occurring antibodies, recognize only one predetermined portion of a molecule; in other words, they are extremely specific in what they will bind to. Monoclonal antibodies are a prime example of targeted therapy.

Mechanisms of action of targeted therapy: [1]

  1. The drug is an antibody that seeks out and kills malignant cells bearing the target antigen; rituximab (trade name: Rituxan), used to treat non-Hodgkin Lymphoma, is one such drug. Antibodies can be combined with cytotoxic (cell-killing) radioisotopes, cytotoxic drugs, and cellular poisons. An example is gemtuzumab (trade name: Mylotarg) combined with calicheamicin (a DNA poison) to target leukemic blood cells.
  2. The drug has a focused mechanism that specifically acts on a well-defined target or biologic pathway that, when interfered with, causes regression or destruction of the malignant process. An example of this is trastuzumab (trade name: Herceptin) for breast cancer.

Two targeted drugs belonging to this second group have been shown to be effective in colorectal cancer: bevacizumab and cetuximab.

Bevacizumab (trade name: Avastin) is a manufactured monoclonal antibody that targets vascular endothelial growth factor (VEGF). VEGF regulates vascular (blood-vessel) proliferation and permeability, and it functions as a survival factor for newly-formed blood vessels. Solid tumours rely on a dense network of blood vessels to grow and to bring the nutrients they need. Bevacizumab has been shown in clinical studies to be effective when used in combination with chemotherapy in first line treatment of metastatic colorectal cancer.

Cetuximab (trade name: Erbitux) is another manufactured monoclonal antibody, developed for the purpose of targeting epidermal growth factor receptor. In normal tissue, epidermal growth factor (EGF) is one of several growth-promoting factors that co-exist with growth-inhibiting factors and regulate cell development. In a cancerous tumour, that balance is disturbed and cell development is accelerated. In some malignant tumours, including some colon cancers, part of that imbalance is generated by EGF. The tumour produces unusually high amounts of receptors to accommodate the growth factor. Cetuximab is designed to "dock" on the receptor and block EGF, thus depriving the cancer of an essential nutrient and adversely affecting tumour cell division, repair, and survival. Cetuximab has been evaluated alone and in combination with various chemotherapeutic agents in a series of clinical studies. At present, it is recognized as useful for patients with metastatic colorectal cancer whose conventional treatment has failed or who have developed intolerance to irinotecan.

Information on Bristol-Myers Squibb Canada’s patient assistance program Access to HopeTM may be found at 1-877-967-6626.

Vectibix™ is the first fully human EGFr monoclonal antibody approved for the treatment of metastatic colorectal cancer. It is a treatment for colorectal cancer patients whose disease has progressed on standard chemotherapy regimens. For certain patients with metastatic colorectal cancer, Vectibix monotherapy was shown in clinical trials to significantly reduce the chance that their metastatic CRC would continue to grow. Vectibix has been commercially available in Canada since July 2008.

Vectibix is the first and only treatment for metastatic colorectal cancer to have data in its approved label showing how to predict which patients are most likely not to benefit from treatment. Before undergoing treatment, a patient can be tested to see whether a certain gene (known as KRAS) has mutated and thus whether Vectibix™ is likely to be effective in this patient.[i] This means that healthcare resources are directed towards those patients who will most likely benefit from the treatment.

Information on Amgen’s oncology patient assistance program VICTORYmay be found at 1-888-706-4717.

Vectibix Newswire press release  Download Adobe Reader- PDF File Reader - Free

Small molecule versus biological drugs



[1] Ross JS, Schenkein DP, Pietrusko R, Rolfe M, Linette GP, Stec J, Stagliano NE, Ginsburg GS, Symmans WF, Pusztai L, Hortobagyi GN. Targeted Therapies for Cancer 2004. Am J Clin Pathol. 2004;122(4):598-609.