Zalcberg John R, Verweij Jaap, Casali Paolo G, Le Cesne Axel, Reichardt Peter, Blay Jean-Yves, Schlemmer Marcus, Van Glabbeke Martine, Brown Michelle, Judson Ian R
Department of Medical Oncology, Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, Vic. 8006, Australia.
Eur J Cancer. 2005 Aug;41(12):1751-7. doi: 10.1016/j.ejca.2005.04.034.
In the EORTC-ISG-AGITG trial 946 patients with advanced gastro-intestinal stromal tumours (GIST) were randomised to receive 400 or 800 mg of imatinib daily. An increase in progression free survival (PFS) was demonstrated for patients randomised to the high-dose arm. Patients randomised to low-dose could cross-over to high-dose upon progression. We evaluated the feasibility, safety and efficacy of this policy. Of the 241 patients available for follow-up, 133 patients (55%) crossed over to high-dose imatinib according to the protocol. Of these patients, 92% had not had a prior dose reduction. The cumulative incidence of subsequent dose reductions after cross-over was 17% after six months with 51% discontinuing therapy without requiring a dose reduction. The extent of anaemia and fatigue increased significantly after cross-over, whilst neutropenia was less severe than during low-dose treatment. Objective responses after cross-over included three patients (2%) with a partial response and 36 (27%) with stable disease. The median PFS after cross-over was 81 days, although 18.1% of patients were still alive and progression free one year after cross-over. We conclude that a cross-over to high-dose imatinib is feasible and safe in GIST patients who progress on low-dose therapy.
在欧洲癌症研究与治疗组织-国际肉瘤协作组-澳大利亚胃肠道肿瘤研究组（EORTC-ISG-AGITG）试验中，946例晚期胃肠道间质瘤（GIST）患者被随机分配，每天接受400毫克或800毫克伊马替尼治疗。结果显示，随机分配至高剂量组的患者无进展生存期（PFS）有所延长。随机分配至低剂量组的患者病情进展时可交叉至高剂量组。我们评估了该策略的可行性、安全性和有效性。在可供随访的241例患者中，133例（55%）按照方案交叉至高剂量伊马替尼治疗组。在这些患者中，92%之前未进行过剂量降低。交叉治疗后六个月内，后续进行剂量降低的累积发生率为17%，51%的患者在无需降低剂量的情况下停止了治疗。交叉治疗后，贫血和疲劳程度显著增加，而中性粒细胞减少症比低剂量治疗期间的情况要轻。交叉治疗后的客观缓解包括3例（2%）部分缓解患者和36例（27%）病情稳定患者。交叉治疗后的中位PFS为81天，尽管18.1%的患者在交叉治疗一年后仍存活且无疾病进展。我们得出结论，对于在低剂量治疗中病情进展的GIST患者，交叉至高剂量伊马替尼治疗是可行且安全的。
