Increased Doses of Gleevec® for Gleevec-Resistant Gastrointestinal Stromal Tumor
According to a recent article published in the European Journal of Cancer, increasing doses of Gleevec® (imatinib) provides anti-cancer activity in patients diagnosed with Gastrointestinal Stromal Tumors (GIST) that had stopped responding to lower doses of the drug.
Gastrointestinal stromal tumors are a rare type of cancer that originate within the gastrointestinal system. These cancers tend to be very aggressive and typically not responsive to treatment with chemotherapy. It is believed that GIST originate within the interstitial cells of Cajal, or the “pacemaker” cells that are in the walls of the gastrointestinal system. Interstitial cells of Cajal are part of the nervous system; they send signals to the gastrointestinal tract, which aid in the movement of food and liquid through the gastrointestinal system.
Gleevec is a biological agent that is approved for the treatment of GIST as well as chronic myeloid leukemia (CML). Gleevec has activity in several biological pathways implicated in the development and/or expression of cancer. It tends to bind to targets within a cell and slows or stops the uncontrolled growth of the cancer cells with certain genetic mutations. Unfortunately, once GIST stops responding to Gleevec, effective treatment options are limited and long-term survival rates are dismal.
Researchers from Europe recently conducted a clinical trial evaluating increased doses of Gleevec in patients with GIST. This trial included 133 patients who were initially treated with 400 mg of Gleevec and ultimately experienced a progression of their cancer. These patients were then treated with 800 mg of Gleevec. Overall, higher doses of Gleevec produced a partial regression of cancer or disease stabilization in nearly 30% of patients. One year following initiation of treatment with 800 mg, approximately 18% of patients were still alive and progression-free. Side effect of higher doses of Gleevec included low levels of red blood cells (anemia) and increased fatigue.
The researchers concluded that patients with advanced GIST who stop responding to treatment with Gleevec may experience a response if treated with higher doses of the drug. Patients with GIST who have stopped responding to therapy may wish to speak with their physician regarding their individual risks and benefits of higher doses of GIST or the participation in a clinical trial evaluating novel therapeutic approaches. Two sources of information regarding ongoing clinical trials include the National Cancer Institute (www.cancer.gov).
Reference: Zalcberg J, Verweijb J, Casali P, et al. Outcome of patients with advanced gastro-intestinal stromal tumours crossing over to a daily imatinib dose of 800mg after progression on 400mg. European Journal of Cancer. 2005; 41: 1751-1757.