Goody Rebecca B, Brade Anthony M, Wang Lisa, Craig Tim, Brierley James, Dinniwell Robert, Wong Rebecca K S, Cho Charles, Kim John, Kassam Zahra, Ringash Jolie, Knox Jennifer J, Dawson Laura A
Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada.
Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Canada.
Radiother Oncol. 2017 May;123(2):234-239. doi: 10.1016/j.radonc.2017.01.018. Epub 2017 Feb 13.
To determine maximum tolerated dose (MTD) and toxicities of sorafenib combined with stereotactic radiotherapy (SBRT) or whole liver radiotherapy (WLRT) in patients with liver metastases.
Eligible patients had unresectable liver metastases. Sorafenib dose was escalated in 2 strata: I - SBRT: effective liver volume irradiated (V)<80% (30-60Gy in 6 fractions); II - WLRT: V>80% (21.6Gy in 6 fractions). Four weeks of sorafenib, with radiotherapy during weeks 2-3, was delivered at 3 escalating dose levels (200-400mg twice daily). Dose limiting toxicity was defined as any grade 3+ liver toxicity, or grade 4+ treatment-related toxicity.
Thirty-three patients were treated: 18 in stratum I (median dose 42Gy), 15 in stratum II. The MTD was not reached. Grade 3+ toxicity was seen in 33% of patients, at a median of 10days. Two deaths from non-classic liver toxicity occurred post WLRT in stratum II. The median overall survival was 22.3 and 5.7months for strata I and II respectively.
Sorafenib and 21.6Gy in 6 fraction WLRT resulted in unacceptably high rates of liver toxicity. Although sorafenib combined with SBRT was tolerable, the observed efficacy does not merit further clinical evaluation.
确定索拉非尼联合立体定向放射治疗（SBRT）或全肝放疗（WLRT）治疗肝转移患者的最大耐受剂量（MTD）及毒性。
符合条件的患者患有不可切除的肝转移瘤。索拉非尼剂量在2个分层中逐步递增：I - SBRT：照射的有效肝体积（V）<80%（6次分割，30 - 60Gy）；II - WLRT：V>80%（6次分割，21.6Gy）。索拉非尼给药4周，在第2 - 3周进行放疗，分3个递增剂量水平（每日2次，200 - 400mg）。剂量限制毒性定义为任何3级以上肝脏毒性或4级以上治疗相关毒性。
33例患者接受治疗：I分层18例（中位剂量42Gy），II分层15例。未达到MTD。33%的患者出现3级以上毒性，中位时间为10天。II分层中2例患者在接受WLRT后因非典型肝脏毒性死亡。I分层和II分层的中位总生存期分别为22.3个月和5.7个月。
索拉非尼与6次分割、21.6Gy的WLRT联合导致肝脏毒性发生率高得令人无法接受。虽然索拉非尼联合SBRT是可耐受的，但观察到的疗效不值得进一步进行临床评估。
