Update on management of GIST and postsurgical use of imatinib

摘要

Abstract: The advent of imatinib is a milestone in the treatment for locally advanced and -metastatic gastrointestinal stromal tumor (GIST) at a dose of 400 mg/day. A higher starting dose of 800 mg/day is recommended only for patients harboring the KIT exon 9 mutation. Studies of imatinib plasma levels are presently ongoing, possibly leading to dose adjustments in the single patient. In localized GIST, complete surgical excision (R0) is considered the standard treatment. Imatinib pretreatment is recommended if R0 surgery is not feasible, or if less mutilating surgery might be achieved by cytoreduction. Whenever surgical morbidity is expected to be an issue, imatinib should be considered even for resectable primary disease in the preoperative setting. Patients with completely resected primary GIST at significant risk of recurrence (based on tumor mitotic rate, size, and location) can be considered for adjuvant imatinib. Dose adjustments could be considered for exon 9 mutant GIST. Imatinib is well tolerated, and its side effects including nonhematologic (periorbital edema, fatigue, nausea, diarrhea, myalgia, skin rash, headache, and abdominal and chest pain) and hematologic (anemia, granulocytopenia, and particularly neutropenia) toxicities are usually mild, although the severity of adverse events increases with dose. While treatment should be continued indefinitely in advanced/metastatic patients, because its interruption is generally followed by relatively rapid tumor progression, the optimal duration of postoperative imatinib therapy is presently not known, even if it is likely that longer disease control will be obtained with longer treatment duration. Patients should be aware that it is not possible thus far to predict the impact of adjuvant therapy on survival. However, the impact on disease control has been dramatic, and imatinib represents a major step forward in the treatment of this rare disease.