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


METHODS
Patients received yttrium-90-labelled ((90)Y) 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/m(2)) with the option to switch to gemcitabine (1000 mg/m(2)) 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.


RESULTS
Fourteen eligible patients were enrolled; ten had primary tumour in situ and eight had liver-only metastases. Patients received a median (90)Y 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.


CONCLUSIONS
SIRT 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.


BACKGROUND
ACTRN12606000015549.
Department of Medical Oncology, Royal Melbourne Hospital, Grattan Street, Parkville, VIC, 3050, Australia. Peter.Gibbs@mh.org.au.|Department of Medical Oncology, Western Hospital, Melbourne, Australia. Peter.Gibbs@mh.org.au.
Peter
P
Gibbs
Department of Medical Oncology, Western Hospital, Melbourne, Australia. Coung.Do@wh.org.au.
Cuong
C
Do
Department of Medical Oncology, Royal Melbourne Hospital, Grattan Street, Parkville, VIC, 3050, Australia. Lara.Lipton@wh.org.au.|Department of Medical Oncology, Western Hospital, Melbourne, Australia. Lara.Lipton@wh.org.au.
Lara
L
Lipton
Sirtex Medical Limited, Sydney, Australia. dcade@sirtex.com.
David N
DN
Cade
Sirtex Medical Limited, Sydney, Australia. mtapner@sirtex.com.
Michael J
MJ
Tapner
Perth Radiological Clinic, Mount Hospital, Perth, Australia. dpri3807@bigpond.net.au.
David
D
Price
Mount Nuclear Medicine, Mount Hospital, Perth, Australia. gbower@isotope.com.au.
Geoff D
GD
Bower
Department of Radiology, Royal Melbourne Hospital, Melbourne, Australia. Richard.Dowling@mh.org.au.
Richard
R
Dowling
Department of Nuclear Medicine, Royal Melbourne Hospital, Melbourne, Australia. Mia.Lichtenstein@mh.org.au.
Meir
M
Lichtenstein
Perth Oncology, Mount Hospital, Perth, Australia. gvh@perthoncology.com.au.
Guy A
GA
van Hazel
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000532:radiotherapy*; D011446:Prospective Studies; D015021:Yttrium Radioisotopes / Q000008:administration & dosage*
D000964:Antimetabolites, Antineoplastic; D015021:Yttrium Radioisotopes; D005472:Fluorouracil