TY - JOUR
T1 - Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib
T2 - Randomised trial
AU - Verweij, Jaap
AU - Casali, Paolo G.
AU - Zalcberg, John
AU - LeCesne, Axel
AU - Reichardt, Peter
AU - Blay, Jean Yves
AU - Issels, Rolf
AU - Van Oosterom, Allan
AU - Hogendoorn, Pancras C.W.
AU - Van Glabbeke, Martine
AU - Bertulli, Rossella
AU - Judson, Ian
N1 - Funding Information:
We thank Haryana Dhillon (Sydney, Australia) and Lidia Mariani (Milan, Italy) for data management, and Michelle Brown for data management coordination. This study was supported by an unrestricted grant from Novartis Oncology.
PY - 2004/9/25
Y1 - 2004/9/25
N2 - Background Imatinib is approved worldwide for use in gastrointestinal stromal tumours (GIST). We aimed to assess dose dependency of response and progression-free survival with imatinib for metastatic GIST. Methods 946 patients were randomly allocated imatinib 400 mg either once or twice a day. Those assigned the once a day regimen who had progression were offered the option of crossover. The primary endpoint was progression-free survival. Analysis was by intention to treat. Findings At median follow-up of 760 days (IQR 644-859), 263 (56%) of 473 patients allocated imatinib once a day had progressed compared with 235 (50%) of 473 who were assigned treatment twice a day (estimated hazard ratio 0·82 [95% CI 0·69-0·98]; p=0·026). Side-effects arose in 465/470 (99%) patients allocated the once daily regimen compared with 468/472 (99%) assigned treatment twice a day. By comparison with the group treated once a day, more dose reductions (77 [16%] vs 282 [60%]) and treatment interruptions (189 [40%] vs 302 [64%]) were recorded in patients allocated the twice daily regimen, but treatment in both arms was fairly well tolerated. 52 (5%) patients achieved a complete response, 442 (47%) a partial response, and 300 (32%) stable disease, with no difference between groups. Median time to best response was 107 days (IQR 58-172). Interpretation If response induction is the only aim of treatment, a daily dose of 400 mg of imatinib is sufficient; however, a dose of 400 mg twice a day achieves significantly longer progression-free survival.
AB - Background Imatinib is approved worldwide for use in gastrointestinal stromal tumours (GIST). We aimed to assess dose dependency of response and progression-free survival with imatinib for metastatic GIST. Methods 946 patients were randomly allocated imatinib 400 mg either once or twice a day. Those assigned the once a day regimen who had progression were offered the option of crossover. The primary endpoint was progression-free survival. Analysis was by intention to treat. Findings At median follow-up of 760 days (IQR 644-859), 263 (56%) of 473 patients allocated imatinib once a day had progressed compared with 235 (50%) of 473 who were assigned treatment twice a day (estimated hazard ratio 0·82 [95% CI 0·69-0·98]; p=0·026). Side-effects arose in 465/470 (99%) patients allocated the once daily regimen compared with 468/472 (99%) assigned treatment twice a day. By comparison with the group treated once a day, more dose reductions (77 [16%] vs 282 [60%]) and treatment interruptions (189 [40%] vs 302 [64%]) were recorded in patients allocated the twice daily regimen, but treatment in both arms was fairly well tolerated. 52 (5%) patients achieved a complete response, 442 (47%) a partial response, and 300 (32%) stable disease, with no difference between groups. Median time to best response was 107 days (IQR 58-172). Interpretation If response induction is the only aim of treatment, a daily dose of 400 mg of imatinib is sufficient; however, a dose of 400 mg twice a day achieves significantly longer progression-free survival.
UR - http://www.scopus.com/inward/record.url?scp=20844433223&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(04)17098-0
DO - 10.1016/S0140-6736(04)17098-0
M3 - Article
C2 - 15451219
AN - SCOPUS:20844433223
SN - 0140-6736
VL - 364
SP - 1127
EP - 1134
JO - The Lancet
JF - The Lancet
IS - 9440
ER -