Conventional Treatment of Colorectal Cancer
Colorectal cancer treatment is adjusted in accordance with the characteristics of each patient's cancer. Surgery is a mainstay for treatment of stage I and most stage II cancers, while stage III and IV cancers are treated with chemotherapy and radiation. Advanced cancers are treated with an aim of reducing symptoms and improving quality of life, as they cannot be cured in most cases.
Surgery is the most common local treatment and usually the first-line treatment for patients diagnosed with localized colorectal cancer. Overall survival rates vary between 55% and 75%, with most recurrences of cancer seen within the first two years of follow-up. For patients whose cancer has not spread to the lymph nodes, survival with surgery alone varies from 75% to 90%. Surgery can also be performed for cancer metastases confined to the liver or lung whenever possible. Surgical removal of metastatic lesions results in long-term survival in a significant number of patients.66
In some cases, the patient will require a colostomy, which is an opening into the colon from outside the body that provides an exit for fecal waste. A colostomy may be temporary or, if the surgery is very extensive, may be permanent. Total colonic resection is sometimes performed as a prophylactic measure for patients with familial polyposis and multiple colon polyps.
Nutritional supplementation and dietary modification should be considered before, during, and after surgery (for more information, refer to the "Cancer Surgery" protocol).
Radiofrequency ablation (RFA) uses radiofrequency energy produced by an electrode that creates temperatures above 60°C (about 140°F) within the tumor, resulting in cancer cell death. RFA is used as an alternative to surgery in patients with inoperable colorectal liver metastases.67,68 Although RFA is unlikely to cure patients, it has a definite role in palliative therapy/relieving symptoms.69
Radiation therapy (also known as radiotherapy) uses targeted, high-energy ionizing X-rays to destroy cancer cells. It is usually used after surgery to eliminate any remaining microscopic cancer cells in the vicinity. However, it may be used prior to surgery to reduce the tumor volume, which enables the removal of tumors previously considered inoperable. Intraoperative radiation therapy (IORT) has the advantage of maximally irradiating the tumor bed while reducing damage to surrounding, normal organ tissue from the field of radiation.
For more information regarding radiation therapy and prevention of its well-known side effects, refer to the chapter "Cancer Radiation Therapy" protocol.
The goal of adjuvant therapy is to eliminate any cancer cells that may have escaped the localized treatment. Adjuvant means "in addition to," and adjuvant therapy is used in combination with surgery and radiation. Several types of adjuvant treatments are usually used for early-stage colorectal cancer. These include chemotherapy, radiotherapy, immunotherapy, nutritional supplementation, and dietary intervention.
Chemotherapy. Chemotherapy uses drugs that can be taken orally or injected intravenously to kill cancer cells. Chemotherapy usually begins four to six weeks after the final surgery, though some oncologists may initiate chemotherapy sooner post-surgery. Typical chemotherapy for colon cancer consists of a combination of drugs that have been found to be the most effective, such as FOLFOX 4 (oxaliplatin, 5-fluorouracil (5-FU), and leucovorin) or FOLFIRI (folinic acid, 5-FU, and irinotecan), followed by FOLFOX6 (folinic acid, 5-FU, and oxaliplatin).70
For many tumors, the potential for eradication using chemotherapy is slight.71 However, chemotherapy using oxaliplatin may make metastatic colorectal cancer patients eligible for liver cancer removal.72 Nevertheless, chemotherapy drugs have many side effects that can damage or destroy some healthy tissues as well; for information on natural compounds that may help to reduce such adverse effects, refer to the "Chemotherapy" protocol.
Chemoresistance is a major hurdle in the treatment of all cancers. This phenomenon occurs when genetic abnormalities make cancer cells resistant to chemotherapeutic drugs. Fortunately, some natural agents may combat chemoresistance.
Studies show that curcumin can inhibit the development of chemoresistance to FOLFOX through effects on insulin-like growth factor 1 receptor (IGF-1R) and/or endothelial growth factor receptor (EGFR).73 When curcumin was used in combination with the targeted drug dasatinib, colon cancer cells' resistance to FOLFOX was eliminated.38 Curcumin has also been shown to sensitize colorectal cancer cells to the lethal effects of radiation therapy.74
Anti-angiogenic therapies stop tumors from forming new blood vessels (eg, by inhibiting VEGF activity) and therefore impede tumor growth. A targeted anti-angiogenic agent, bevacizumab (Avastin), which is a humanized monoclonal antibody targeting circulating VEGF, prolonged survival of metastatic colorectal cancer patients who had inoperable tumors.75 Interestingly, in patients with metastatic colorectal cancer, the addition of Avastin to irinotecan, fluorouracil, and leucovorin improves survival regardless of the level of VEGF expression.76 However, side effects from Avastin can be severe and improvements in survival seldom result in cures for advance cases.