Colorectal cancer radiation therapy

Oxaliplatin is a novel platinum compound that has shown promising activity in colorectal cancers. It has been associated with up to 60% response rates when used as front-line therapy, and 25-50% response rates in relapsed or refractory colorectal cancer. It is currently being evaluated in a Phase I study with 5-FU and radiation in patients with locally advanced esophageal cancer (NCI T99-0061). 

Chemotherapy and radiation therapy play an important role in the management of colorectal carcinoma. Significant improvements in tumor control and overall survival have been demonstrated with the use of combined-modality therapy in several randomized clinical trials performed over the past 25 yr. This chapter reviews the role of adjuvant chemotherapy and radiation therapy for colon and rectal cancer. Issues surrounding chemoradiation for rectal cancer, including sphincter preservation, total mesorectal excision, local excision, and newer chemotherapy agents, are also discussed. 

Adjuvant chemotherapy involves the use of antineoplastic drugs when surgery or radiation therapy has eradicated the primary tumor but historical experience with similar patients indicates a high risk of relapse due to micrometastases. Adjuvant chemotherapy should employ drugs that are known to be effective in the treatment of advanced stages of the particular tumor being treated. Adjuvant chemotherapy has played a major role in the cure of several types of childhood cancers as well as breast cancer, colorectal cancer, and osteosarcoma in adults. 

Cetuximab is indicated for the treatment of head, neck and colorectal cancers, and in combination with radiation therapy it is used for the treatment of squamous cell carcinoma (locally or regionally advanced) of the head and neck. However, in patients with recurrent or metastatic squamous cell carcinoma of the head and neck whose response to the previous platinum-based therapy has not been positive, it is not given in combination with radiation therapy and is administered alone. Generally, a dose of 400 mg/m2 is initially administered in combination with radiation therapy followed by a maintenance dose of 250 mg/m2 and is administered 1 h... 

Treatment modalities for colorectal cancer include surgery, XRT, chemotherapy, immunotherapy, and new targeted molecular therapies. Surgery is the most important and deflnitive procedure associated with cure radiation therapy can be used to improve curability following surgical resection and to reduce symptoms and complications... 

CEA is expressed in a variety of carcinomas, particularly of the gastrointestinal tract (e.g., Crohn s disease, inflammatory bowel disease, post-radiation therapy to the bowel) and can be detected in the serum. lMMU-4 is specific for the classical 200000-Da CEA that is found predominantly on the cell membrane. " Tc-CEA-Scan complexes the circulating CEA and binds to CEA on the cell surface. Imaging efficacy and safety have been evaluated in four clinical trials to evaluate the presence, location, and extent of colorectal cancer, primarily in the liver and extrahepatic abdominal and pelvic regions. 

COMBINATION THERAPY Higher response rates are seen when 5-FU is used in combination with other agents, such as cyclophosphamide and methotrexate (breast cancer), cisplatin (head and neck cancer), and with oxaliplatin or irinotecan in colon cancer. The combination of 5-FU and oxaliplatin or irinotecan has become the standard first-hne treatment for patients with metastatic colorectal cancer. The use of 5-FU in combination regimens has improved survival in the adjuvant treatment for breast cancer, and with oxaliplatin and leucovorin, for colorectal cancer. 5-FU also is a potent radiation sensitizer. Beneficial effects also have been reported when combined with irradiation for cancers of the esophagus, stomach, pancreas, cervix, anus, and head and neck. 5-FU is used widely with very favorable results for the topical treatment of premalignant keratoses of the skin and multiple superficial basal cell carcinomas. 

Lim L, Gibbs P, Yip D, Shapiro JD, Dowling R, Smith D, Little A, Bailey W, Liechtenstein M (2005a) A prospective evaluation of treatment with Selective Internal Radiation Therapy (SIR-spheres) in patients with unresectable liver metastases from colorectal cancer previously treated with 5-FU based chemotherapy. BMC Cancer 5 132... 

Robertson ]M, McGinn CJ, Walker S et al (1997) A phase I trial of hepatic arterial bromodeoxyuridine and conformal radiation therapy for patients with primary hepatobiliary cancers or colorectal liver metastases. Int J Radiat Oncol Biol Phys 39 1087-1092... 

Given the encouraging safety and therapeutic benefit of °Y in both primary and metastatic liver disease, there is an opportunity to explore its application in combination with other available therapies. Studies to assess the potential synergistic therapeutic benefit of °Y and known radio-sensitizers in both metastatic breast and colorectal cancer are warranted. Combination capecitabine and Y present a low toxicity option for breast cancer patients. The potential to improve hepatic tumor response via the synergistic action of selective uptake of 5-FU in the presence of radiation warrants further investigation. °Y in combination with 5-FU, FUDR and capecitabine in colorectal metastases to the liver require further study. Given the potential for super irradiation of liver parenchyma in the presence of these agents, carefully controlled Phase I dose escalation studies are required. 

Bellomi M, Petralia G, Sonzogni A, Zampino MG, Rocca A (2007) CT perfusion for the monitoring of neoadjuvant chemotherapy and radiation therapy in rectal carcinoma initial experience. Radiology 244 486-93 Benson AB III, Choti MA, Cohen AM et al. (2000) National Comprehensive Cancer Network. NCCN Practice Guidelines for Colorectal Cancer. Oncology (Williston Park) 14 203-212... 

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