Imatinib Improves Survival in GISTs
According to a recent article published in The Lancet, imatinib (formerly STI-571) is well tolerated and significantly improves survival in patients with advanced gastrointestinal stromal tumors.
Gastrointestinal stromal tumors (GISTs) are a unique subset of cancers that are most often located in the stomach, but can arise anywhere in the gastrointestinal tract. GISTs arise from the cells of Cajal, or the “pacemaker” cells of the gastrointestinal tissue. Standard treatment for GISTs includes the surgical removal of the cancer, chemotherapy and/or radiation therapy. However, GISTs tends to be aggressive in nature and resistant to radiation and chemotherapy, with only 4.8% of cases responsive to chemotherapy. Patients with advanced GIST have an average survival of 9 to 20 months following standard treatment.
The majority of GISTs have a mutation (alteration) within a protein called KIT. KIT is involved in biological processes that facilitate the growth and multiplication of healthy cells. Normally, this growth process is kept under strict control; however, KIT mutations involved with GISTs lead to excessive, uncontrolled multiplication of cancer cells.
Imatinib is a relatively new biologic agent that has recently been approved by the FDA for the treatment of chronic myelogenous leukemia. It is currently being evaluated in clinical trials for the treatment of various cancers, including GIST. One function of imatinib involves binding to KIT that contains mutations involved in GISTs. This binding action stops or slows the excessive growth of the cancer cells caused by the mutated KIT and has also been implicated in the direct death of cells containing mutated KIT.
Researchers from the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group recently conducted a clinical trial further evaluating imatinib including increasing doses, in 36 patients with advanced GIST. Patients were divided into groups receiving different doses: 400 milligrams (mg) once daily, 300 mg twice daily, 400 mg twice daily or 500 mg twice daily. Patients receiving 500 mg twice daily had dose-limiting side-effects including severe nausea, vomiting, edema or rash. Following therapy, overall, 25 patients achieved a reduction in their cancer and all but 4 patients in this trial achieved inhibition of cancer progression. Twenty-nine patients are still receiving imatinib more than 9 months following initiation of treatment. Side effects tended to subside after the first 8 weeks of treatment.
The researchers conducting this study report that imatinib at 400 mg twice daily is well tolerated and has significant long-term activity in patients with advanced GIST. These results are extremely important as GISTs are difficult to treat and typically do not respond well to standard therapies. Clinical trials will further evaluate imatinib in patients with GIST and other cancers with a mutated KIT protein. Patients diagnosed with GIST may wish to speak with their physician about the risks and benefits of participating in a clinical trial evaluating imatinib. Two sources of information regarding ongoing clinical trials include comprehensive, easy-to-use listing services provided by the National Cancer Institute (cancer.gov). (The Lancet, Vol 358, No 9291, pp 1421-1423, 2001)