PARAGON II - A single arm multicentre phase II study of neoadjuvant therapy using irinotecan bead in patients with resectable liver metastases from colorectal cancer
PARAGON II - A single arm multicentre phase II study of neoadjuvant therapy using irinotecan bead in patients with resectable liver metastases from colorectal cancer
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DOI：
10.1016/j.ejso.2016.07.142
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发表时间：
2016-12-01
期刊：
影响因子：
3.8
通讯作者：
Poston, G. J.
中科院分区：
文献类型：
--
作者：
Jones, R. P.;Malik, H. Z.;Poston, G. J.
目的：结直肠癌肝转移切除术（CRLM）后，围手术期化疗可获得3年无进展生存优势，但与显著毒性相关。使用载有伊立替康的药物洗脱PVA微球（DEBIRI）进行化学栓塞，可将药物直接持续递送至肿瘤，最大限度地提高反应，同时最大限度地减少全身暴露。这个II期单臂研究探讨了DEBIRI的安全性和可行性切除CRLM.Methods：可切除CRLM患者接受肺叶DEBIRI手术前1个月，与放射学终点的近停滞。该试验的主要终点为肿瘤可切除性（RO切除）。次要终点包括安全性，病理肿瘤反应和总survival.Results：40例患者接受DEBIRI，伊立替康的中位剂量为103毫克（范围64-175毫克）。死亡率较低（2.5%，CTCAE 2级），无全身化疗毒性证据。所有患者均进行了手术，其中38例进行了切除（95%，RO切除率74%）。30-术后1天死亡率为5%（n = 2），死亡均与TACE无关。66个病灶被切除，在77.3%的靶病灶中观察到组织学主要或完全病理学缓解。中位随访40.6个月，12例患者（34.3%）死于复发性疾病，中位总生存期为50.9个月。术后1、3、5年OS分别为93%、78%、49%。DEBIRI单次治疗的肿瘤病理学反应和中位总生存期与全身新辅助化疗后的结果相当。(C)2016年6月，作者。由Elsevier Ltd.发布。这是CC BY-NC-ND许可下的开放获取文章。
Purpose: Perioperative chemotherapy confers a 3-year progression free survival advantage following resection of colorectal liver metastases (CRLM), but is associated with significant toxicity. Chemoembolisation using drug eluting PVA microspheres loaded with irinotecan (DEBIRI) allows sustained delivery of drug directly to tumour, maximising response whilst minimising systemic exposure. This phase II single arm study examined the safety and feasibility of DEBIRI before resection of CRLM.Methods: Patients with resectable CRLM received lobar DEBIRI 1 month prior to surgery, with a radiological endpoint of near stasis. The trial had a primary end-point of tumour resectability (RO resection). Secondary end-points included safety, pathologic tumour response and overall survival.Results: 40 patients received DEBIRI, with a median dose of 103 mg irinotecan (range 64-175 mg). Morbidity was low (2.5%, CTCAE grade 2) with no evidence of systemic chemotoxicity. All patients proceeded to surgery, with 38 undergoing resection (95%, RO resection rate 74%). 30-day post-operative mortality was 5% (n = 2), with neither death TACE related. 66 lesions were resected, with histologic major or complete pathologic response seen in 77.3% of targeted lesions. At median follow up of 40.6 months, 12 patients (34.3%) had died of recurrent disease with a median overall survival of 50.9 months. Nominal 1, 3 and 5-year OS was 93, 78 & 49% respectively.Conclusions: Resection after neoadjuvant DEBIRI for CRLM is feasible and safe. Single treatment with DEBIRI resulted in tumour pathologic response and median overall survival comparable to that seen after systemic neoadjuvant chemotherapy. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.