TY - JOUR
T1 - A randomized, phase II study of preoperative plus postoperative Imatinib in GIST
T2 - Evidence of rapid radiographic response and temporal induction of tumor cell apoptosis
AU - McAuliffe, John C.
AU - Hunt, Kelly K.
AU - Lazar, Alexander J.F.
AU - Choi, Haesun
AU - Qiao, Wei
AU - Thall, Peter
AU - Pollock, Raphael E.
AU - Benjamin, Robert S.
AU - Trent, Jonathan C.
N1 - Funding Information:
ACKNOWLEDGEMENTS This work was supported by an institutional Physician-Scientist Award (J.C.T. and A.J.F.L.), NIH/ NCI grant 1K23CA109060-02 (JCT), the Amschwand Sarcoma Cancer Foundation (J.C.T.), NIH TL1 RR 024147 from the Center of Clinical and Translational Sciences at The University of Texas-Houston Health Science Center (J.C.M.), and NIH/NCI grant K12 CA090891 (J.C.M.). The DNA Sequencing Core Facility is supported by NCI Cancer Center Support Grant CA-16672. J.C.T. also acknowledges an unrestricted investigator-initiated grant from Nov-artis Pharmaceuticals, Inc.
PY - 2009/4
Y1 - 2009/4
N2 - Gastrointestinal stromal tumor (GIST) is the most common sarcoma arising in the gastrointestinal (GI) tract. Imatinib mesylate (imatinib) is efficacious in treating advanced and metastatic GIST. Patients undergoing resection of GIST realize a highly variable median disease-free survival (DFS). In the absence of prospective data, we conducted a randomized, phase II study to assess the safety and efficacy of preoperative and postoperative imatinib for the treatment of GIST. Nineteen GIST patients undergoing surgical resection were randomized to receive 3, 5, or 7 days of preoperative imatinib (600 mg daily). Patients received postoperative imatinib for 2 years. Perioperative adverse events were compared with those in an imatinib-naïve historical control. The efficacy of imatinib was assessed by 18fluorodeoxyglucose positron emission tomography (18FDG-PET), dynamic computed tomography (dCT), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and DFS. Imatinib did not affect surgical morbidity as compared with an imatinib-naïve cohort (p ≥ 0.1). Most patients responded to preoperative imatinib by 18FDG-PET and dCT (69% and 71%, respectively). Tumor cell apoptosis increased by an average of 12% (range 0-33%) and correlated with the duration of preoperative imatinib (p = 0.04). Median DFS of patients treated with surgery and imatinib was 46 months (range 10-46 months). Tumor size was a predictor of recurrence after postoperative imatinib (p = 0.02). Imatinib appears to be safe and may be considered for patients undergoing surgical resection of their GIST. Radiographic response and tumor cell apoptosis occur within the first week of imatinib therapy.
AB - Gastrointestinal stromal tumor (GIST) is the most common sarcoma arising in the gastrointestinal (GI) tract. Imatinib mesylate (imatinib) is efficacious in treating advanced and metastatic GIST. Patients undergoing resection of GIST realize a highly variable median disease-free survival (DFS). In the absence of prospective data, we conducted a randomized, phase II study to assess the safety and efficacy of preoperative and postoperative imatinib for the treatment of GIST. Nineteen GIST patients undergoing surgical resection were randomized to receive 3, 5, or 7 days of preoperative imatinib (600 mg daily). Patients received postoperative imatinib for 2 years. Perioperative adverse events were compared with those in an imatinib-naïve historical control. The efficacy of imatinib was assessed by 18fluorodeoxyglucose positron emission tomography (18FDG-PET), dynamic computed tomography (dCT), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and DFS. Imatinib did not affect surgical morbidity as compared with an imatinib-naïve cohort (p ≥ 0.1). Most patients responded to preoperative imatinib by 18FDG-PET and dCT (69% and 71%, respectively). Tumor cell apoptosis increased by an average of 12% (range 0-33%) and correlated with the duration of preoperative imatinib (p = 0.04). Median DFS of patients treated with surgery and imatinib was 46 months (range 10-46 months). Tumor size was a predictor of recurrence after postoperative imatinib (p = 0.02). Imatinib appears to be safe and may be considered for patients undergoing surgical resection of their GIST. Radiographic response and tumor cell apoptosis occur within the first week of imatinib therapy.
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U2 - 10.1245/s10434-008-0177-7
DO - 10.1245/s10434-008-0177-7
M3 - Article
C2 - 18953611
AN - SCOPUS:62149141753
SN - 1068-9265
VL - 16
SP - 910
EP - 919
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
IS - 4
ER -