Refractory metastatic colorectal cancer is an all too common situation for patients and caregivers. The search for available clinical trials can be confusing and frustrating for many patients. This website is designed to provide some guidance to patients looking for clinical trials of novel agents that may provide benefit, and help in deciphering the terminology of clinical trials, including definitions of Phase I, IB, II, IIB, and III trials .
First, some definitions. Colorectal cancer is a broad term that includes patients with colon cancer or rectal cancer. Although the treatments for early stage disease is different for colon and rectal cancer, they share very similar biology and are commonly treated as one entity when the disease is metastatic. Metastatic disease refers to cancer that has spread to distant regions of the body, most commonly to the liver, lungs, or abdominal lining (peritoneum). When cancer that starts in the colon or rectum spreads to other locations, the cancer is still called colorectal cancer, and is not called by the name of its metastatic location. For example, colorectal cancer that spreads to the liver is called metastatic colorectal cancer. It is not called liver cancer, which is a separate type of cancer with very different treatments. Patients who have previously been treated with the available chemotherapy agents and had the disease grow in size despite treatment are considered to have refractory cancer.
This website is specifically designed to keep an updated list of available Phase II studies for patients whose colorectal cancer is refractory to all available FDA-approved agents, accessibly by from the links above.
Frequently Asked Questions
What are the FDA approved agents for metastatic colorectal cancer? (These are the ones available from your oncologist outside of a clinical trial)
- 5-fluorouracil (5-FU), a DNA damaging chemotherapy
- Capecitabine, an oral form of 5-FU with equal efficacy
- Leucovorin, a modulator of 5-FU without activity by itself
- Irinotecan, a DNA damaging chemotherapy
- Oxaliplatin, a DNA damaging chemotherapy
- Bevacizumab, an inhibitor of blood vessel growth factors (VEGF)
- Cetuximab, an inhibitor of cancer cell growth factors (EGFR)
- Panitumumab, another inhibitor of cancer cell growth factors (EGFR)
How do I know if I am refractory to all available agents?
Your oncologist will work with you to provide combinations of these chemotherapies that are the best balance of efficacy and side effects, possibly as part of a clinical trial. However, after two or three combinations of these chemotherapy drugs, it is unlikely that additional regimens will provide benefit and patients should consider clinical trial options. Some patients whose tumors contain certain gene mutations don't benefit from cetuximab and pantimumab, as the gene mutations are known to cause the tumor to be refractory to the treatment. Some of the therapies provide overlapping mechanisms of action. For example, use of capecitabine alone after your tumor has progressed on 5-FU is very unlikely to provide benefit. Similarly, use of panitumumab after the failure of cetuximab therapy is not beneficial. In some situations your oncologist may recommend continuing some chemotherapy that has previously failed in combination with other therapies you have not previously received.
Importantly, some patients appropriately have their oxaliplatin stopped due to neuropathy (nerve damage) during an earlier regimen, with out having evidence that the tumor has grown during the oxaliplatin therapy. Once the nerve damage improves, it may be possible to return to the oxaliplatin therapy and derive some additional benefit.
Where to I find information about clinical trials? The most up to date resource for this is the website maintained by the National Cancer Institute, ClinicalTrials.gov. However, many patients find this site difficult to navigate and lacking sufficient information to critically judge the available trials. For more information, see our guide to interpreting ClinicalTrials.gov. Once you have identified some potential trials, look though our guide to evaluating a clinical trial .
When should I consider enrolling in a clinical trial? There are clinical trials available for adjuvant therapy for colon and rectal cancer, as well as initial therapy and second-line therapy for metastatic colorectal cancer. If such trials are available to you, you should consider enrolling in them, as they provide access to the latest potential advances in the field and additional research nurse involvement in your care that would not otherwise be available. However, after a patient's cancer grows, it is not uncommon for there to be limited treatment options available. In this situation, clinical trials may be the only available option for treating your disease. Given the effort likely to be involved in traveling to a specialized center for such trials, it is important that patients understand the options available to them. This website is designed to be one such tool that can be used with your oncologist to formulate the best plan for your treatment. However, clinical trials are not the right option for all patients, and your oncologist can help discuss the risks and benefits of this.
About the author of this guide.
Disclaimer: These comments are not a treatment recommendation, but reflect the author's opinion and survey of agent under investigation. These comments do not reflect knowledge of specific trial results that are not currently published or publically presented. These comments reflect the personal opinion of the author and are not the opinion of MD Anderson Cancer Center. Likewise, this site is not formally affiliated with MD Anderson Cancer.