Phase 1 Trial of Sorafenib and Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma
Phase 1 Trial of Sorafenib and Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma
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DOI：
10.1016/j.ijrobp.2015.11.048
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发表时间：
2016-03-01
影响因子：
7
通讯作者：
Dawson, Laura A.
中科院分区：
文献类型：
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作者：
Brade, Anthony M.;Ng, Sylvia;Dawson, Laura A.
目的：确定索拉非尼的最大耐受剂量之前，期间和之后立体定向体部放射治疗（SBRT）在hepatocellular carinoma.Methods和Materials：符合条件的患者有局部晚期Child-Pugh A级HCC，显示东部肿瘤协作组性能状态0-1，并没有资格进行标准的局部区域治疗。索拉非尼剂量递增分为2个分层：（1）低有效辐照肝体积（veff）< 30%和（2）高veff 30%-60%。索拉非尼（400 mg每日一次=剂量水平1）给药12周，第2周和第3周给予6个分次SBRT，12周后在耐受情况下递增至全剂量（400 mg每日两次）。结果：16例患者（4例低veff，中位剂量51戈伊; 12例高veff，中位剂量33戈伊）接受了2个剂量水平的索拉非尼治疗。这些患者中75%为巴塞罗那临床肝癌C期，63%有门静脉主干分支侵犯。在低veff分层中，在接受SBRT和索拉非尼400 mg治疗的4例患者中未观察到剂量限制性毒性（DLT）。在高Veff地层中：接受索拉非尼400 mg治疗的3例可评价患者中有2例发生DLT（SBRT后分别为51天和27天，3级大肠出血和4级肠梗阻）。剂量水平-1（200 mg每日一次）的6例可评价患者中有1例在第5周发生3级肿瘤破裂。中位总生存期和在外地的局部进展没有被高veff strature.Conclusions：观察到显着的毒性在高veff层，并同时SBRT索拉非尼不建议外的临床试验。(C)2016由Elsevier Inc.出版
Purpose: To determine the maximally tolerated dose of sorafenib delivered before, during, and after stereotactic body radiation therapy (SBRT) in hepatocellular carinoma (HCC).Methods and Materials: Eligible patients had locally advanced Child-Pugh class A HCC, showed Eastern Cooperative Oncology Group performance status 0-1, and were ineligible for standard local-regional therapies. Sorafenib was dose escalated in 2 strata: (1) low effective irradiated liver volume (veff) < 30% and (2) high veff 30% to 60%. Sorafenib (400 mg daily = dose level 1) was administered for 12 weeks, with 6 fractions SBRT delivered weeks 2 and 3, and escalation to full dose (400 mg twice daily) after 12 weeks as tolerated. Standard 3 + 3 cohorts with dose escalation of sorafenib were planned.Results: Sixteen patients (4 low veff, median dose 51 Gy; 12 high veff, median dose 33 Gy) were treated at 2 sorafenib dose levels. Of those patients 75% were had Barcelona Clinic Liver Cancer stage C, and 63% had main branch portal vein invasion. In the low veff stratum, no dose-limiting toxicities (DLTs) were observed in 4 patients treated with SBRT and sorafenib 400 mg. Inb the high veff stratum: 2 of 3 evaluable patients treated with sorafenib 400 mg experienced DLT (grade 3 large bowel bleed and grade 4 bowel obstruction 51 and 27 days, respectively, after SBRT). One of 6 evaluable patients at dose level -1 (200 mg once daily) experienced a grade 3 tumor rupture at week 5. Median overall survival and in-field local progression have not been the high veff stratum.Conclusions: Significant toxicity was observed in the high veff stratum, and concurrent SBRT with sorafenib is not recommended outside a clinical trial. (C) 2016 Published by Elsevier Inc.