Adjuvant therapy of colorectal cancer
In about three fourth of all patients who present to the physician, complete surgical removal of the entire tumor in an attempt to cure the disease may be feasible. Almost 50 percent of all these patients who get surgery with a curative intention will die from recurrence of colorectal cancer. The primary reason for recurrence of colorectal cancer in these patients is the residual cancer that remains in the body despite the best surgical efforts. The role of adjuvant therapy is to reduce the residual disease left in the body after surgical procedure in an attempt to improve the cure rates. Adjuvant therapy of colorectal cancer may include chemotherapy, radiation therapy or both.
Since adjuvant therapy of colon cancer and rectal cancer may be different, both of these treatments will be explained separately.
Adjuvant therapy of colon cancer
Chemotherapy is the primary mode of adjuvant therapy for patients with colon cancer. There is no good evidence for beneficial effects of adjuvant chemotherapy for patients with colorectal cancer who have lymph node negative disease (stage I an stage II). On the other hand the beneficial effects of adjuvant chemotherapy for patients who have involvement of lymph nodes (stage III) are well proven. The following are active adjuvant therapy options for patients with stage III colorectal cancer:
Fluorouracil (5-FU) plus leucovorin (folinic acid)
A combination of fluorouracil (5-FU) and leucovorin (folinic acid) is the most commonly used adjuvant chemotherapy for patients with stage III colon cancer. Folinic acid is not a chemotherapy drug. Leucovorin (folinic acid) works as a biochemical modulator that increases efficacy of fluorouracil. Both of these medications are given through the intravenous route.
Capecitabine (Xeloda) gained FDA approval as an adjuvant therapy for stage III colorectal cancer in June 2005. This drug is in the form of a pill and is administered orally. This drug is equally as effective as the combination of fluorouracil and leucovorin for prevention of recurrence.
Fluorouracil, leucovorin plus oxaliplatin
Addition of oxaliplatin to fluorouracil and leucovorin has been shown to improve progression free survival (Ref: NEJM 2004; 350: 2343-2351). Addition of oxaliplatin increases risk of some side effects like neuropathy. This combination does not produce improvement in overall survival compared to fluorouracil and leucovorin.
Other newer drugs that are active in metastatic colon cancer are actively undergoing clinical trials in the setting of adjuvant therapy. These drugs include irinotecan, Bevacizumab, and Cetuximab.
Adjuvant therapy for rectal cancer
Rectal cancer tend to fail locally more often compared to colon cancer. Local recurrence of the disease in the pelvis may cause complications with involvement of other pelvic structures like bladder, ureters, bones and nerves. Symptoms of local recurrence of rectal cancer may vary depending on the site and extent of the local recurrence. These patients may have no symptoms at all or may have excruciating pain because of the involvement of the nervous structures inside the pelvis. Because of increased risk of local recurrence in the case of rectal cancer, radiation therapy is often incorporated into the adjuvant therapy. Like in colon cancer, patients who have stage I and stage II rectal cancers may not be candidates for adjuvant chemotherapy. The following are the adjuvant therapy options for patients with rectal cancer:
Most commonly employed adjuvant therapy for rectal cancer consists of continuous infusion of fluorouracil (5-FU) using a 24-hour infusion pump, throughout the course of radiation therapy. This is usually followed a period chemotherapy alone, just like the adjuvant therapy of colon cancer.
Capecitabine (Xeloda is increasingly used for the adjuvant therapy of rectal cancer in place of the continuous infusion fluorouracil (combined with radiation). Once radiation therapy is complete, these patients may continue to receive capecitabine (Xeloda) alone for some more months.
Other newer drugs
Just like the adjuvant treatment of colon cancer newer drugs are actively investigated in the setting of rectal cancer as well. These new drugs include oxaliplatin, irinotecan, Bevacizumab, and Cetuximab.