Phase II trial of selective internal radiation therapy and systemic chemotherapy for liver-predominant metastases from pancreatic adenocarcinoma

BMC Cancer

Research Article

Lara Lipton¹  Peter Gibbs¹  Cuong Do²  Meir Lichtenstein³  Richard Dowling⁴  Geoff D. Bower⁵  Guy A. van Hazel⁶  David Price⁷  David N. Cade⁸  Michael J. Tapner⁸ 

[1] Department of Medical Oncology, Royal Melbourne Hospital, Grattan Street, 3050, Parkville, VIC, Australia;Department of Medical Oncology, Western Hospital, Melbourne, Australia;Department of Medical Oncology, Western Hospital, Melbourne, Australia;Department of Nuclear Medicine, Royal Melbourne Hospital, Melbourne, Australia;Department of Radiology, Royal Melbourne Hospital, Melbourne, Australia;Mount Nuclear Medicine, Mount Hospital, Perth, Australia;Perth Oncology, Mount Hospital, Perth, Australia;Perth Radiological Clinic, Mount Hospital, Perth, Australia;Sirtex Medical Limited, Sydney, Australia;

关键词: Advanced;    Liver;    Metastases;    Pancreas;    Radioembolization;    SIRT;   

DOI  :  10.1186/s12885-015-1822-8

 received in 2014-02-25, accepted in 2015-10-16,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThis prospective, open-label phase II study assessed the impact of liver-directed therapy with selective internal radiation therapy (SIRT) and systemic chemotherapy on progression-free survival (PFS) in liver-dominant metastatic pancreatic adenocarcinoma.MethodsPatients received yttrium-90-labelled (90Y) resin microspheres (SIR-Spheres; Sirtex Medical Limited, Sydney, Australia) as a single procedure on day 2 of the first weekly cycle of 5-fluorouracil (5FU; 600 mg/m2) with the option to switch to gemcitabine (1000 mg/m2) after 8 weeks of 5FU. Statistical analysis was conducted using Microsoft Excel (Microsoft Corporation, Redmond, Washington, USA). The primary endpoint of the study was PFS in the liver, with a median of ≥16 weeks defined as the threshold for clinical significance. PFS and overall survival (OS) were summarised by the Kaplan-Meier method using non-parametric estimates of the survivor function.ResultsFourteen eligible patients were enrolled; ten had primary tumour in situ and eight had liver-only metastases. Patients received a median 90Y activity of 1.1 GBq and 8 weekly doses of 5FU; seven patients received a median of two doses of gemcitabine. Disease control in the liver was 93 % (two confirmed partial responses [PR], one unconfirmed PR, ten stable disease). Median reduction in cancer antigen 19–9 was 72 %. Median PFS was 5.2 months in the liver, which met the primary endpoint of the study, and 4.4 months at any site. PFS was prolonged in those with a resected primary compared with patients with primary in situ (median 7.8 vs. 3.4 months; p = 0.017). Median OS was 5.5 months overall and 13.6 months in patients with a resected primary. Grade 3/4 adverse events occurred in eight (57 %) patients during days 0–60. There was one sudden death and another patient who died from possible treatment-related liver failure 7.0 months after SIRT.ConclusionsSIRT and chemotherapy appears to be an effective treatment for liver metastases from pancreatic cancer, likely to be of most benefit in selected patients with a resected primary tumour and liver only disease. Significant toxicity was observed and the safety of this approach in patients with metastatic pancreatic cancer will need to be confirmed in subsequent studies. Further study is warranted with SIRT and modern chemotherapies.Trial registrationACTRN12606000015549

【 授权许可】

CC BY   
© Gibbs et al. 2015