BACKGROUND: Imatinib inhibits the KIT and PDGFR tyrosine kinases, resulting in its notable antitumor activity in gastrointestinal stromal tumor (GIST). We previously reported the early results of a multi-institutional prospective trial (RTOG 0132) using neoadjuvant/adjuvant imatinib either in primary resectable GIST or as a planned preoperative cytoreduction agent for metastatic/recurrent GIST. METHODS.: Patients with primary GIST (≥5 cm, group A) or resectable metastatic/recurrent GIST (≥2 cm, group B) received neoadjuvant imatinib (600 mg/day) for approximately 2 months and maintenance postoperative imatinib for 2 years. We have now updated the clinical outcomes including progression-free survival, disease-specific survival, and overall survival at a median follow-up of 5.1 years, and we correlate these end points with duration of imatinib therapy. RESULTS: Sixty-three patients were originally entered (53 analyzable: 31 in group A and 22 in group B). Estimated 5-year progression-free survival and overall survival were 57% in group A, 30% in group B; and 77% in group A, 68% in group B, respectively. Median time to progression has not been reached for group A and was 4.4 years for group B. In group A, in 7 of 11 patients, disease progressed >2 years from registration; 6 of 7 patients with progression had stopped imatinib before progression. In group B, disease progressed in 10 of 13 patients>2 years from registration; 6 of 10 patients with progressing disease had stopped imatinib before progression. There was no significant increase in toxicity compared with our previous short-term analysis. CONCLUSIONS: This long-term analysis suggests a high percentage of patients experienced disease progression after discontinuation of 2-year maintenance imatinib therapy after surgery. Consideration should be given to studying longer treatment durations in intermediate- to high-risk GIST patients.
BACKGROUND:Imatinib inhibits the KIT and PDGFR tyrosine kinases, resulting in its notable antitumor activity in gastrointestinal stromal tumor (GIST). We previously reported the early results of a multi-institutional prospective trial (RTOG 0132) using neoadjuvant/adjuvant imatinib either in primary resectable GIST or as a planned preoperative cytoreduction agent for metastatic/recurrent GIST. METHODS.: Patients with primary GIST (≥5 cm, group A) or resectable metastatic/recurrent GIST (≥2 cm, group B) received neoadjuvant imatinib (600 mg/day) for approximately 2 months and maintenance postoperative imatinib for 2 years. We have now updated the clinical outcomes including progression-free survival, disease-specific survival, and overall survival at a median follow-up of 5.1 years, and we correlate these end points with duration of imatinib therapy. RESULTS: Sixty-three patients were originally entered (53 analyzable: 31 in group A and 22 in group B). Estimated 5-year progression-free survival and overall survival were 57% in group A, 30% in group B; and 77% in group A, 68% in group B, respectively. Median time to progression has not been reached for group A and was 4.4 years for group B. In group A, in 7 of 11 patients, disease progressed >2 years from registration; 6 of 7 patients with progression had stopped imatinib before progression. In group B, disease progressed in 10 of 13 patients>2 years from registration; 6 of 10 patients with progressing disease had stopped imatinib before progression. There was no significant increase in toxicity compared with our previous short-term analysis. CONCLUSIONS: This long-term analysis suggests a high percentage of patients experienced disease progression after discontinuation of 2-year maintenance imatinib therapy after surgery. Consideration should be given to studying longer treatment durations in intermediate- to high-risk GIST patients.
Authors: Maria Debiec-Rychter; Raf Sciot; Axel Le Cesne; Marcus Schlemmer; Peter Hohenberger; Allan T van Oosterom; Jean-Yves Blay; Serge Leyvraz; Michel Stul; Paolo G Casali; John Zalcberg; Jaap Verweij; Martine Van Glabbeke; Anne Hagemeijer; Ian Judson Journal: Eur J Cancer Date: 2006-04-18 Impact factor: 9.162
Authors: John R Zalcberg; Jaap Verweij; Paolo G Casali; Axel Le Cesne; Peter Reichardt; Jean-Yves Blay; Marcus Schlemmer; Martine Van Glabbeke; Michelle Brown; Ian R Judson Journal: Eur J Cancer Date: 2005-08 Impact factor: 9.162
Authors: S Bonvalot; H Eldweny; C Le Péchoux; D Vanel; P Terrier; A Cavalcanti; C Robert; N Lassau; A Le Cesne Journal: Ann Surg Oncol Date: 2006-12 Impact factor: 5.344
Authors: Chandrajit P Raut; Matthew Posner; Jayesh Desai; Jeffrey A Morgan; Suzanne George; David Zahrieh; Christopher D M Fletcher; George D Demetri; Monica M Bertagnolli Journal: J Clin Oncol Date: 2006-05-20 Impact factor: 44.544
Authors: Robert H I Andtbacka; Chaan S Ng; Courtney L Scaife; Janice N Cormier; Kelly K Hunt; Peter W T Pisters; Raphael E Pollock; Robert S Benjamin; Michael A Burgess; Lei L Chen; Jonathan Trent; Shreyaskumar R Patel; Kevin Raymond; Barry W Feig Journal: Ann Surg Oncol Date: 2007-01 Impact factor: 5.344
Authors: Imran Hassan; Y Nancy You; Roman Shyyan; Eric J Dozois; Thomas C Smyrk; Scott H Okuno; Cathy D Schleck; David O Hodge; John H Donohue Journal: Ann Surg Oncol Date: 2007-11-14 Impact factor: 5.344
Authors: Charles D Blanke; Cathryn Rankin; George D Demetri; Christopher W Ryan; Margaret von Mehren; Robert S Benjamin; A Kevin Raymond; Vivien H C Bramwell; Laurence H Baker; Robert G Maki; Michael Tanaka; J Randolph Hecht; Michael C Heinrich; Christopher D M Fletcher; John J Crowley; Ernest C Borden Journal: J Clin Oncol Date: 2008-02-01 Impact factor: 44.544
Authors: Charles D Blanke; George D Demetri; Margaret von Mehren; Michael C Heinrich; Burton Eisenberg; Jonathan A Fletcher; Christopher L Corless; Christopher D M Fletcher; Peter J Roberts; Daniela Heinz; Elisabeth Wehre; Zariana Nikolova; Heikki Joensuu Journal: J Clin Oncol Date: 2008-02-01 Impact factor: 44.544
Authors: Brian K Bednarski; Dejka M Araujo; Min Yi; Keila E Torres; Alexander Lazar; Jonathan C Trent; Janice N Cormier; Peter W T Pisters; Dina Chelouche Lev; Raphael E Pollock; Barry W Feig; Kelly K Hunt Journal: Ann Surg Oncol Date: 2014-03-18 Impact factor: 5.344
Authors: Ser Yee Lee; Brian K P Goh; Eran Sadot; Rahul Rajeev; Vinod P Balachandran; Mithat Gönen; T Peter Kingham; Peter J Allen; Michael I D'Angelica; William R Jarnagin; Daniel Coit; Wai Keong Wong; Hock Soo Ong; Alexander Y F Chung; Ronald P DeMatteo Journal: Ann Surg Oncol Date: 2016-09-13 Impact factor: 5.344