Julia Draznin Maltzman, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: February 28, 2005
= Julia Draznin Matlzman, MD, Senior Editor
WS = Dr. Weijing Sun
Dr. Weijing Sun, Assistant Professor of Medicine at the University of Pennsylvania, the Director of Upper GI and Pancreatic-biliary-hepatic Cancer Group and the Associate Director of the GI Cancer Program, is an expert in gastrointestinal cancers. OncoLink was able to obtain his thoughts and visions on the many new therapeutic developments for colon cancer in honor of March, colorectal cancer awareness month.
OncoLink: Tell me a little about the history and the evolution of the chemotherapy for the treatment of colon cancer.
WS: Medical treatment of colon cancer had made little progress for the past half a century until the early 1990’s when an explosion in therapeutics took the field to a new level. A drug by the name of fluorouracil was the cornerstone of medical treatment for almost 50 years.
The combination of fluorouracil with leucovorin, a folinic acid, increased the overall survival of an average of 5-10% at five years for patients with advanced colon cancer.
For individuals with earlier stage disease, for example those who have had their cancer surgically resected but were found to have lymph node involvement, six to eight months of chemotherapy with fluorouracil and leucovorin could decrease the risk of recurrence of colon cancer by 10-20%. The benefit for those individuals whose cancer did not yet spread to the lymph nodes was somewhat less clear because of smaller benefit.
In past several years, two new drugs irinotecan and oxaliplatin brought the treatment of colon cancer to a different level. With their introduction the response rates for advanced disease doubled and clearly increased progression-free and overall survival. Irinotecan combined with fluorouracil increased median overall survival by about three moths. Three months may sound very modest, but this was a significant improvement for individuals with metastatic disease. Combination of oxaliplatin with fluorouracil was found to have even a further benefit.
New revolutionary treatments for colorectal cancer have entered into the field in past two years. Thirty years ago, a surgeon named Judah Folkman proposed that new blood vessel formation was important for cancer growth. However, until very recently, drugs that block new blood vessel formation had little benefit in solid tumors. A large study looked at a new agent -- bevacizumab (Avastin). This monoclonal antibody blocks the vascular endothelial growth factors (VEGF), which are important for the formation of new blood vessels. When added to the traditional chemotherapy of fluorouracil, leucovorin, and irinotecan, it was found to increase response rates and progression free survival in patients with untreated metastatic colon cancer. More importantly, this new combination was able to prolong life by five months. Some of the more recent trials were able to show that bevacizumab could be also combined with oxaliplatin for a similar benefit.
The next drug to enter the arena was cetuximab (Erbitux), an antibody to the epidermal growth factor receptor (EGFR). Clinical trials showed it to have further benefit for those patients who have been heavily treated previously. This too was revolutionary as we now have a drug to offer people who were otherwise close to or have already exhausted other options.
OncoLink: With so many options, how does one decide on what to give a patient? Or do you do it sequentially?
WS: The fundamental goal for treating patients is trying to control their disease, improve patients’ quality of life, and eventually prolong their life for those with metastatic or advanced disease. So treatment choice must be based on what is the best option we have plus consideration of the patient’s overall condition. These factors include other chronic diseases, general performance status, and to some degree, patient preference. For example, irinotecan may cause much diarrhea and dehydration which may not be the best option for an individual with preexisting gastro-intestinal problems. On the other hand, oxaliplatin may cause neuropathy and may not be the first line choice for those patients with a preexisting neuropathy such as seen in some diabetics. The anti-angiogenesis agent may cause blood clot related events such as cardiac infarction or stroke and bowel perforation. This must be considered prior to giving therapy to those patients with high risk for these events.
OncoLink: What do you know about vaccine therapy and is it a possibility for colon cancer?
WS: Some data did suggest that a vaccine approach may have some efficacy in this disease. These trials, however, were very small. To date, there have been no large confirmatory studies to prove a benefit and this remains a highly experimental tool in colon cancer.
OncoLink: Can colon cancer become a chronic disease much like diabetes? Could one live with colon cancer for a long time?
WS: The answer is unequivocally yes. Many patients are already living five years and beyond after their diagnosis. For patients with advanced disease our ultimate goal is long-term control with a good quality of life.
OncoLink: Prevention is still better than any treatment, right?
WS: Absolutely. As a physician I recommend that everyone follow the screening guidelines so that we diagnose the disease early while it is still curable by surgical means. This is especially true for those patients with a strong family history and other high risk factors.
OncoLink: What is in the future for colon cancer treatment?
WS: What we need to do more of is to diagnose early and treat early in order to increase the cure rates.
For those in whom the disease has already spread at the time of diagnosis and therapy is necessary, we need to continue to try and develop more targeted and individualized therapy. By this I mean, give therapy that would only destroy the cancer and leave the other cells unharmed (targeted therapy). Knowing in advance which patients are likely to respond to which therapy would allow us to offer potentially toxic therapy only to those people who would derive a benefit (individualized therapy). People who are unlikely to benefit would not be offered the treatment and thus be spared the potential side effects.
In the setting of advanced, metastatic disease, minimizing toxicity and maintaining a good quality of life are arguably the most important aspects of treatment.
On a final note, as more effective treatment emerges, we need to be mindful of cost. The cost of research, development, and management can rise quickly and substantially. Keeping costs down is essential as this enables scares resources to be available for anyone who may need them.