Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033
Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033
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DOI：
10.1200/jco.2007.13.4452
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发表时间：
2008-02-01
影响因子：
45.3
通讯作者：
Borden, Ernest C.
中科院分区：
文献类型：
--
作者：
Blanke, Charles D.;Rankin, Cathryn;Borden, Ernest C.
PurposeTo评估潜在的差异无进展或总生存期时，伊马替尼甲磺酸盐给予患者不可治愈的胃肠道间质瘤（GIST）在一个标准剂量（400毫克，每天）与高剂量（400毫克，每天两次）Patients and MethodsPatients with metastatic or surgically unremotable GIST were eligible for this phase III open-label clinical trial.在登记时，患者被随机分配到标准或高剂量伊马替尼组，并进行密切的随访。如果客观进展发生在实体瘤的反应评价标准，标准剂量组的患者可以重新注册到试验中，并接受高剂量伊马替尼regimentation.ResultsSeven一百四十六名患者在美国和加拿大的148个中心的先进GIST入组到这项试验在9个月。中位随访时间为4.5年，标准剂量组患者的中位无进展生存期为18个月，接受高剂量伊马替尼治疗的患者为20个月。中位总生存期分别为55和51个月。客观缓解率、无进展生存期或总生存期无统计学显著差异。在标准剂量伊马替尼治疗进展后，33%的交叉至高剂量伊马替尼治疗方案的患者实现了客观缓解或疾病稳定。有更多的3级，4级和5级毒性注意到高剂量伊马替尼arm.ConclusionThis试验证实了伊马替尼作为主要的全身治疗的有效性与不可治愈的胃肠道间质瘤患者，但没有显示出任何优势，以更高的剂量治疗。以400 mg/天开始治疗并考虑在疾病进展时剂量递增似乎是合理的。
PurposeTo assess potential differences in progression-free or overall survival when imatinib mesylate is administered to patients with incurable gastrointestinal stromal tumors ( GIST) at a standard dose ( 400 mg daily) versus a high dose ( 400 mg twice daily).Patients and MethodsPatients with metastatic or surgically unresectable GIST were eligible for this phase III open-label clinical trial. At registration, patients were randomly assigned to either standard or high-dose imatinib, with close interval follow-up. If objective progression occurred by Response Evaluation Criteria in Solid Tumors, patients on the standard-dose arm could reregister to the trial and receive the high-dose imatinib regimen.ResultsSeven hundred forty-six patients with advanced GIST from 148 centers across the United States and Canada were enrolled onto this trial in 9 months. With a median follow-up of 4.5 years, median progression-free survival was 18 months for patients on the standard-dose arm, and 20 months for those receiving high-dose imatinib. Median overall survival was 55 and 51 months, respectively. There were no statistically significant differences in objective response rates, progression-free survival, or overall survival. After progression on standard-dose imatinib, 33% of patients who crossed over to the high-dose imatinib regimen achieved either an objective response or stable disease. There were more grade 3, 4, and 5 toxicities noted on the high-dose imatinib arm.ConclusionThis trial confirms the effectiveness of imatinib as primary systemic therapy for patients with incurable GIST but did not show any advantage to higher dose treatment. It appears reasonable to initiate therapy with 400 mg daily and to consider dose escalation on progression of disease.