Bone and Soft Tissue Sarcomas

Annals of Surgical Oncology

, Volume 16, Issue 4, pp 910-919

Open Access This content is freely available online to anyone, anywhere at any time.

A Randomized, Phase II Study of Preoperative plus Postoperative Imatinib in GIST: Evidence of Rapid Radiographic Response and Temporal Induction of Tumor Cell Apoptosis

  • John C. McAuliffeAffiliated withMD/PhD Program, The University of Texas-HoustonDepartment of Sarcoma Medical Oncology, The University of Texas M. D. Anderson Cancer CenterSarcoma Research Center, The University of Texas M. D. Anderson Cancer Center
  • , Kelly K. HuntAffiliated withDepartment of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center
  • , Alexander J. F. LazarAffiliated withSarcoma Research Center, The University of Texas M. D. Anderson Cancer CenterDepartment of Pathology, The University of Texas M. D. Anderson Cancer Center
  • , Haesun ChoiAffiliated withDepartment of Diagnostic Radiology, The University of Texas M. D. Anderson Cancer Center
  • , Wei QiaoAffiliated withDepartment of Biostatistics, The University of Texas M. D. Anderson Cancer Center
  • , Peter ThallAffiliated withDepartment of Biostatistics, The University of Texas M. D. Anderson Cancer Center
  • , Raphael E. PollockAffiliated withSarcoma Research Center, The University of Texas M. D. Anderson Cancer CenterDepartment of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center
  • , Robert S. BenjaminAffiliated withDepartment of Sarcoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center
  • , Jonathan C. TrentAffiliated withDepartment of Sarcoma Medical Oncology, The University of Texas M. D. Anderson Cancer CenterSarcoma Research Center, The University of Texas M. D. Anderson Cancer Center Email author 

Abstract

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.