According to an article recently published in the Journal of Clinical Oncology, the addition of chemotherapy to pre-operative radiation therapy improves anti-cancer responses in rectal cancer, potentially allowing for greater surgical removal of the cancer.

The American Cancer Society estimates that over 40,000 people will be diagnosed with rectal cancer in the United States in 2005. The rectum includes the last six inches of the large intestine and is the portion of the large intestine located between the colon (upper half of large intestine) and the anus (lowest portion of large intestine that leads to the outside of the body). Although rectal cancer is often referred to in conjunction with colon cancer as “colorectal cancer”, treatment for rectal cancer often varies from that of colon cancer. One factor that determines differences in treatment of colon and rectal cancer is the location of the cancer. Surgery to remove rectal cancer can often injure the sphincter (circular muscle that is responsible for voluntary control of defecation). If the sphincter is injured, patients can become fecally incontinent for the remainder of their lives. Therefore, special consideration is given to surgical procedures that will remove as much cancer as possible without compromising sphincter control.

One way to minimize injury from rectal cancer surgery is to shrink the cancer prior to surgery. The cancer size can be drastically reduced with the use of radiation therapy and/or chemotherapy prior to surgery (pre-operative or neoadjuvant therapy). In addition to allowing for more complete removal of cancer with surgery while keeping tissue injury to a minimum, the administration of treatment prior to surgery allows for therapy to begin killing cancer cells that may have spread in the body. However, the optimal neoadjuvant regimen has not yet been confirmed. The debate of whether radiation alone or radiation plus chemotherapy improves outcomes in patients with this disease has not yet been resolved.

Researchers affiliated with the European Organization for Research and Treatment of Cancer (EORTC) recently conducted a clinical trial to directly compare neoadjuvant radiation therapy alone to neoadjuvant radiation therapy plus chemotherapy in patients with operable rectal cancer. The study included 1,011 patients. Approximately half were treated with neoadjuvant radiation therapy alone, and the other half were treated with neoadjuvant radiation therapy plus the chemotherapy agent 5-fluorouracil. Following neoadjuvant therapy, patients treated with radiation plus chemotherapy had significantly smaller cancers, a decreased spread of cancer to surrounding lymph nodes, nerves, and venous (blood-carrying) structures than patients treated with radiation therapy alone.

The researchers concluded that these preliminary results indicate that neoadjuvant radiation plus chemotherapy appears to reduce cancer spread to nearby structures as well as reduce the size of cancer compared to neoadjuvant radiation therapy alone in patients diagnosed with operable rectal cancer. Longer follow-up is necessary to determine if this treatment strategy will translate into improved long-term outcomes for these patients. Patients with operable rectal cancer may wish to speak with their physician regarding their individual risks and benefits of participating in a clinical trial further evaluating neoadjuvant therapy strategies or other novel therapeutic approaches. Two sources of information regarding ongoing clinical trials include the National Cancer Institute (www.cancer.gov) and www.cancerconsultants.com .

Reference: Bosset J-F, Calais G, Mineur L, et al. Enhanced Tumorocidal Effect of Chemotherapy With Preoperative Radiotherapy for Rectal Cancer: Preliminary Results-EORTC 22921. *Journal of Clinical Oncology.*2005; 23: 5620-5627.

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