Gibbs Peter, Gebski Val, Van Buskirk Mark, Thurston Kenneth, Cade David N, Van Hazel Guy A
Royal Melbourne Hospital, Melbourne, Victoria, Australia.
BMC Cancer. 2014 Dec 1;14:897. doi: 10.1186/1471-2407-14-897.
In colorectal cancer (CRC), unresectable liver metastases are linked to poor prognosis. Systemic chemotherapy with regimens such as FOLFOX (combination of infusional 5-fluorouracil, leucovorin and oxaliplatin) is the standard first-line treatment. The SIRFLOX trial was designed to assess the efficacy and safety of combining FOLFOX-based chemotherapy with Selective Internal Radiation Therapy (SIRT or radioembolisation) using yttrium-90 resin microspheres (SIR-SpheresR; Sirtex Medical Limited, North Sydney, Australia).
METHODS/DESIGN: SIRFLOX is a randomised, multicentre trial of mFOLFOX6 chemotherapy+/-SIRT as first-line treatment of patients with liver-only or liver-predominant metastatic CRC (mCRC). The trial aims to recruit adult chemotherapy-naive patients with proven liver metastases with or without limited extra-hepatic disease, a life expectancy of >=3 months and a WHO performance status of 0-1. Patients will be randomised to receive either mFOLFOX6 or SIRT+mFOLFOX6 (with a reduced dose of oxaliplatin in cycles 1-3 following SIRT). Patients in both arms can receive bevacizumab at investigator discretion. Protocol chemotherapy will continue until there is unacceptable toxicity, evidence of tumour progression, complete surgical resection or ablation of cancerous lesions, or the patient requests an end to treatment. The primary endpoint of the SIRFLOX trial is progression-free survival (PFS). Secondary endpoints include: PFS in the liver; tumour response rate (liver and any site); site of tumour progression; health-related quality of life; toxicity and safety; liver resection rate; and overall survival. Assuming an increase in the median PFS from 9.4 months to 12.5 months with the addition of SIRT to mFOLFOX6, recruiting >=450 patients will be sufficient for 80% power and 95% confidence.
The SIRFLOX trial will establish the potential role of SIRT+standard systemic chemotherapy in the first-line management of mCRC with non-resectable liver metastases.
SIRFLOX ClinicalTrials.gov identifier: NCT00724503. Registered 25 July 2008.
在结直肠癌（CRC）中，无法切除的肝转移与预后不良相关。采用FOLFOX（持续输注5-氟尿嘧啶、亚叶酸钙和奥沙利铂的联合方案）等方案进行全身化疗是标准的一线治疗方法。SIRFLOX试验旨在评估基于FOLFOX的化疗联合使用钇-90树脂微球（SIR-SpheresR；Sirtex Medical Limited，澳大利亚北悉尼）进行选择性内放射治疗（SIRT或放射性栓塞）的疗效和安全性。
方法/设计：SIRFLOX是一项随机、多中心试验，比较mFOLFOX6化疗±SIRT作为仅肝转移或肝转移为主的转移性结直肠癌（mCRC）患者的一线治疗。该试验旨在招募未接受过化疗的成年患者，这些患者已证实存在肝转移，有无局限性肝外疾病均可，预期寿命≥3个月，世界卫生组织体能状态为0-1。患者将被随机分配接受mFOLFOX6或SIRT+mFOLFOX6（SIRT后第1-3周期奥沙利铂剂量降低）。两组患者均可根据研究者的判断接受贝伐单抗治疗。方案化疗将持续进行，直至出现不可接受的毒性、肿瘤进展的证据、癌灶的完全手术切除或消融，或患者要求终止治疗。SIRFLOX试验的主要终点是无进展生存期（PFS）。次要终点包括：肝脏的PFS；肿瘤缓解率（肝脏和任何部位）；肿瘤进展部位；健康相关生活质量；毒性和安全性；肝切除率；以及总生存期。假设在mFOLFOX6基础上加用SIRT可使中位PFS从9.4个月增加到12.5个月，招募≥450例患者将足以达到80%的检验效能和95%的置信度。
SIRFLOX试验将确定SIRT+标准全身化疗在无法切除肝转移的mCRC一线治疗中的潜在作用。
SIRFLOX在ClinicalTrials.gov的标识符：NCT00724503。于2008年7月25日注册。
