摘要
Background Imatinib is approved worldwide for use in gastrointestinal stromal tumours (GIST).We aimed to assess dose dependency of response and progression-f ree survival with imatinib for metastatic GIST. Methods 946 patients were random ly 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 pri mary 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 pa tients 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 a rms was fairly well tolerated. 52 (5%) patients achieved a complete response, 4 42 (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). Interpr etation 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 sig nificantly longer progression-free survival.
Background Imatinib is approved worldwide for use in gastrointestinal stromal tumours (GIST).We aimed to assess dose dependency of response and progression-f ree survival with imatinib for metastatic GIST. Methods 946 patients were random ly 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 pri mary 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 pa tients 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 a rms was fairly well tolerated. 52 (5%) patients achieved a complete response, 4 42 (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). Interpr etation 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 sig nificantly longer progression-free survival.
