OBJECTIVES: Self-reported progression was evaluated as a predictor of survival in patients with metastatic gastrointestinal stromal tumor (GIST). METHODS: This is a follow-up of an open cohort study of Life Raft Group (LRG) members with a diagnosis of KIT-positive metastatic GIST receiving imatinib from May 2000-December 2007 reporting their subjective response to therapy by completion of an internet-based questionnaire. Subjects received >or= 1 year of imatinib and reported an initial positive response. Members reporting stable disease or progression were excluded. Self-reported progression-free survival (srPFS) was compared with overall survival (OS) and analyzed by starting and last reported dose. RESULTS: One hundred sixty-nine subjects reported a mean starting dose of 527.8+/-177.9 mg/d at a mean age of 53.8+/-11.6 years at initial diagnosis. Of those reporting progression, 66% died versus 11% of those not reporting progression (P < 0.0001). When analyzed by last reported dose, a median srPFS benefit of 27.3 months was observed for the >400 mg/d group (P = 0.0017). Sixty-two percent of subjects who initiated therapy at >400 mg/d reported a dose reduction. When analyzed by last reported dose, a significant benefit in OS (P = 0.0229) and srPFS (P = 0.0069) was observed for subjects taking 600 over 400 mg/d. CONCLUSIONS: srPFS strongly correlated with OS. Significant advantages were observed when last reported dose was considered, as was higher daily dose. These observations suggest that careful escalation to intermediate daily doses should be investigated further for its potential to reduce the incidence and severity of adverse events, but also as a strategy against developing secondary resistance to imatinib.
OBJECTIVES: Self-reported progression was evaluated as a predictor of survival in patients with metastatic gastrointestinal stromal tumor (GIST). METHODS: This is a follow-up of an open cohort study of Life Raft Group (LRG) members with a diagnosis of KIT-positive metastatic GIST receiving imatinib from May 2000-December 2007 reporting their subjective response to therapy by completion of an internet-based questionnaire. Subjects received >or= 1 year of imatinib and reported an initial positive response. Members reporting stable disease or progression were excluded. Self-reported progression-free survival (srPFS) was compared with overall survival (OS) and analyzed by starting and last reported dose. RESULTS: One hundred sixty-nine subjects reported a mean starting dose of 527.8+/-177.9 mg/d at a mean age of 53.8+/-11.6 years at initial diagnosis. Of those reporting progression, 66% died versus 11% of those not reporting progression (P < 0.0001). When analyzed by last reported dose, a median srPFS benefit of 27.3 months was observed for the >400 mg/d group (P = 0.0017). Sixty-two percent of subjects who initiated therapy at >400 mg/d reported a dose reduction. When analyzed by last reported dose, a significant benefit in OS (P = 0.0229) and srPFS (P = 0.0069) was observed for subjects taking 600 over 400 mg/d. CONCLUSIONS: srPFS strongly correlated with OS. Significant advantages were observed when last reported dose was considered, as was higher daily dose. These observations suggest that careful escalation to intermediate daily doses should be investigated further for its potential to reduce the incidence and severity of adverse events, but also as a strategy against developing secondary resistance to imatinib.
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: Wim G Goettsch; Steffan D Bos; Nancy Breekveldt-Postma; Mariel Casparie; Ron M C Herings; Pancras C W Hogendoorn Journal: Eur J Cancer Date: 2005-11-15 Impact factor: 9.162
Authors: Ian Judson; Peiming Ma; Bin Peng; Jaap Verweij; Amy Racine; Eugenio Donato di Paola; Martine van Glabbeke; Sasa Dimitrijevic; Michelle Scurr; Herlinde Dumez; Allan van Oosterom Journal: Cancer Chemother Pharmacol Date: 2004-12-09 Impact factor: 3.333
Authors: Jayesh Desai; Sridhar Shankar; Michael C Heinrich; Jonathan A Fletcher; Christopher D Fletcher; Judi Manola; Jeffrey A Morgan; Christopher L Corless; Suzanne George; Kemal Tuncali; Stuart G Silverman; Annick D Van den Abbeele; Eric van Sonnenberg; George D Demetri Journal: Clin Cancer Res Date: 2007-09-15 Impact factor: 12.531
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: Clifford D Mol; Douglas R Dougan; Thomas R Schneider; Robert J Skene; Michelle L Kraus; Daniel N Scheibe; Gyorgy P Snell; Hua Zou; Bi-Ching Sang; Keith P Wilson Journal: J Biol Chem Date: 2004-04-29 Impact factor: 5.157
Authors: Michael C Heinrich; Christopher L Corless; Anette Duensing; Laura McGreevey; Chang-Jie Chen; Nora Joseph; Samuel Singer; Diana J Griffith; Andrea Haley; Ajia Town; George D Demetri; Christopher D M Fletcher; Jonathan A Fletcher Journal: Science Date: 2003-01-09 Impact factor: 47.728
Authors: Michael C Heinrich; Christopher L Corless; George D Demetri; Charles D Blanke; Margaret von Mehren; Heikki Joensuu; Laura S McGreevey; Chang-Jie Chen; Annick D Van den Abbeele; Brian J Druker; Beate Kiese; Burton Eisenberg; Peter J Roberts; Samuel Singer; Christopher D M Fletcher; Sandra Silberman; Sasa Dimitrijevic; Jonathan A Fletcher Journal: J Clin Oncol Date: 2003-12-01 Impact factor: 44.544