Treatment updates from the 2009 ASCO Gastrointestinal Cancers Symposium.
In January, researchers, oncologists, and other physicians from around the world gathered in San Francisco for the 2009 American Society of Clinical Oncology Gastrointestinal Cancers Symposium. The research presented included a wide spectrum of diseases, including colorectal cancer, and covered a variety of topics, including prevention, treatment, and the management of side effects. Several notable studies stood out:
Antibodies targeting the epidermal growth factor receptor, specifically Erbitux (cetuximab) and Vectibix (panitumumab), are frequently used in the treatment of metastatic colorectal cancer. These agents can significantly improve outcomes for patients with tumors that express the normal form (also called wild-type) of the KRAS gene. However, the most common side effects associated with these drugs are skin rash, which can be moderate to severe in some cases, and can affect quality of life, increase risk of infection, and may ultimately delay treatment.
Edith Mitchell, MD, of the Jefferson Kimmel Comprehensive Cancer Center in Philadelphia, presented results from the STEPP (Skin Toxicity Evaluation Protocol with Panitumumab) study, which compared skin treatment at the start of Vectibix as a preventive measure versus skin treatment after reactions occurred. The study found that a daily regimen consisting of steroids, sunscreen, skin moisturizers, and 100 mg of the antibiotic doxycycline twice daily was more effective when given at the start of Vectibix therapy, significantly reducing the incidence of skin rash, and interestingly, diarrhea. Importantly, this regimen did not appear to interfere with the effectiveness of the drug therapy.
Read more about rash management in A Rash of Good News from the Winter 2007 issue of CURE.
Sandostatin LAR (octreotide long-acting release formulation) is commonly used to relieve symptoms such as diarrhea and flushing associated with the production of hormones by certain neuroendocrine tumors, which are somewhat rare cancers that involve the gastrointestinal tract and other areas. However, researchers did not know whether the suppression of the effects of these hormones might also have an anti-cancer impact.
Results from the randomized PROMID study were presented by Rudolph Arnold, MD, of Phillips University in Germany. The study compared the effect of Sandostatin LAR with placebo in 85 patients with relatively rare metastatic neuroendocrine tumors in the midgut. Sandostatin LAR dramatically delayed the time to tumor progression, from six months to 14.3 months. At six months, two-thirds of patients treated with Sandostatin LAR had stable disease, compared with 37 percent of patients who received placebo.
Outcomes were better in patients with smaller or less widespread tumors, emphasizing the importance of early detection and treatment, and in those who had undergone resection of their primary tumor.
For patients with metastatic colorectal cancer that has spread only to the liver, surgical resection can potentially be curative. Sometimes, though, the metastases may be too large, or may be in a location that makes surgery difficult or impossible. In some of these cases, preoperative chemotherapy may shrink the metastases enough to allow a surgeon to operate successfully. However, the optimal length of treatment is not known, and the duration of preoperative therapy can vary depending on the tumor response.
In a study by Daria Zorzi, MD, and colleagues at M.D. Anderson Cancer Center in Houston, the connection between length of preoperative chemotherapy and outcome was investigated in 219 patients. They found that longer treatment (nine or more cycles) with FOLFOX-based combination chemotherapy did not improve response rates and increased the chance of developing postoperative complications, such as liver damage compared to shorter treatment (eight or fewer cycles).
In addition, patients who received Avastin (bevacizumab) with their chemotherapy had better response rates than those treated only with chemotherapy, regardless of length of treatment. These results suggest that compared with historical data, Avastin improves response rates compared with chemotherapy alone.
A study presented by Gunnar Folprecht, MD, of the University Hospital Dresden in Germany, evaluated the addition of Erbitux to either FOLFOX or FOLFIRI regimens before surgery for treatment in patients with colorectal cancer who had inoperable liver metastases. They found that for patients with KRAS wild-type tumors, both combinations were highly effective, with a 70 percent response rate.
Importantly, surgeons were now able to operate in approximately 40 percent of cases, and were able to completely remove the liver metastases 34 percent of the time. The response rate was only 43 percent in patients with KRAS-mutant tumors, reinforcing the need to test for KRAS mutation status before using Erbitux in patients with colorectal cancer. Common side effects included rash, neutropenia, and diarrhea.