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Understanding Cancer Series
Credit: NCI, Bill Branson (Photographer)
Colorectal cancer is the third most frequently diagnosed cancer in both men and women and the second leading cause of cancer-related mortality in the United States. That said, rates of new cases and rates of death from colorectal cancer have been declining this decade. According to the Annual Report to the Nation authored by researchers from the National Cancer Institute (NCI), the Centers for Disease Control and Prevention (CDC), the American Cancer Society (ACS), and the North American Association of Central Cancer Registries (NAACCR), if Americans increase use of screening, adopt more favorable health behaviors and pair that with optimal treatment outcomes, overall colorectal cancer mortality rates could decrease by 50 percent by the year 2020.
The importance of colorectal cancer screening has made headlines for many years, raising awareness and leading to higher rates of colonoscopies from 2000 through 2008. This increase in screening levels has played a significant role in decreasing colorectal cancer mortality. Along with screening, advances in colorectal cancer treatment have played a pivotal role in reducing mortality rates. Surgery, traditional chemotherapy and newer targeted therapies have been important tools in treating this disease.
Credit: NCI, John Crawford (Photographer)
Surgery continues to be the primary treatment option for colorectal cancer patients and colon/rectal resection has been the standard procedure for cancer primarily contained in the colon/rectum. Studies have shown that laparoscopic surgery has been more successful than traditional open surgery in reducing recovery time for patients, but studies are still underway to determine the overall benefit of one technique over the other. “Specific risk factors and expertise inform a surgeon’s decision of what procedure to perform,” says Jack Welch, M.D., Ph.D, head of GI and Neuroendocrine Cancers Therapeutics in the the Clinical Therapy Evaluation Program (CTEP), within NCI’s Division of Cancer Treatment and Diagnosis.
There are four stages of colorectal cancer, with stage I being the easiest to treat and stage IV being the most difficult. Stage II and III colorectal cancers offer the greatest challenge in choosing which treatment modalities to use.
Advances in chemotherapy over the past decade have lead to a change in treatment practice standards for colorectal cancer, increasing the cure rate and prolonging survival rates for patients with advanced disease. For several decades, chemotherapy regimens based on the drug fluorouracil (5-FU) have been part of the treatment for stage III colon cancer. Adding other agents to a backbone of 5-FU has further advanced treatment in both the adjuvant and advanced setting. FOLFOX, a combined chemotherapy regimen, which includes 5-FU, leucovorin and oxaliplatin (other chemotherapy drugs) is a classic example. FOLFOX produced higher response rates in patients and also demonstrated superior clinical benefit in patients with advanced colorectal cancer when compared to 5-FU plus leucovorin alone or 5-FU plus oxaliplatin alone.
Chemotherapy is not typically recommended in the treatment of stage II colorectal cancer because the side effects from treatment outweigh the benefit derived for most patients. However, some clinical studies are underway with the aim of identifying stage II patients who are at particularly high risk for recurrence of their disease, and giving them treatment to prevent the cancer from coming back.
Targeted therapies also offer great promise in the fight against colorectal cancer. In 2004, the FDA approved bevacizumab (Avastin®, Genentech, Inc.) as a first-line treatment or initial treatment for patients with metastatic colorectal cancer. Then in 2006, the FDA granted approval as a second-line treatment as well. This meant that bevacizumab could be used if the current first-line treatment was not successful. These recommendations were based on findings that showed better overall survival in patients receiving bevacizumab plus FOLFOX when compared to receiving FOLFOX alone. Bevacizumab is an antiangiogenic agent; it inhibits tumor growth by blocking the formation of new blood vessels. According to Welch, “clinical trials have shown that bevacizumab improves outcome in metastatic disease, but in a recent phase III study of adjuvant colon cancer, the addition of bevacizumab to standard therapy did not increase disease free survival.” Therefore, while targeted therapies have shown promise, there is no guarantee that they will work in every treatment setting, highlighting the need for clinical trials to prove benefit.
“Similarly, patients with [some types of] advanced colorectal tumors have benefitted from cetuximab or panitumumab (two other types of targeted therapies). These targeted agents typically have toxicities that do not strongly overlap those of traditional chemotherapy, which opens up new ways to combine these agents with existing chemotherapy,” Welch says.
Improving treatment and its dissemination will most likely have the earliest impact on colorectal cancer mortality. “Finding the right combination therapy for the right patient and tailoring treatment to individuals with a specific genetic background or to specific types of tumors will help improve treatment outcomes in the future,” says Welch. “Biomarkers are things that we can measure from blood or tissue samples. We hope that by studying biomarkers in individual patients, we will be able to predict how that person will respond to a specific type of treatment and then tailor the therapy accordingly.” Moreover, “improvements in imaging technology and methods will allow us to determine earlier if our treatment is being effective. Biomarkers and imaging will help us make decisions more quickly, more accurately, and on an individual-by-individual level.”
Currently, the National Cancer Institute is sponsoring 357 clinical trials addressing colorectal cancer treatment and prognosis. Many of these trials now include targeted agents as part of the treatment regimen. For more information please visit http://www.cancer.gov/clinicaltrials.
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