Selective Internal Radiation Therapy (SIRT) with yttrium-90 resin microspheres plus standard systemic chemotherapy regimen of FOLFOX versus FOLFOX alone as first-line treatment of non-resectable liver metastases from colorectal cancer

The SIRFLOX study

SIRFLOX Study Group

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background: 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-Spheres® 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-native 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. Discussion: 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. Trial registration: SIRFLOX ClinicalTrials.gov identifier: NCT00724503. Registered 25 July 2008.

Original languageEnglish (US)
Article number897
JournalBMC Cancer
Volume14
Issue number1
DOIs
StatePublished - Dec 1 2014
Externally publishedYes

Fingerprint

Yttrium
Microspheres
Colorectal Neoplasms
Radiotherapy
Neoplasm Metastasis
Drug Therapy
oxaliplatin
Liver
Disease-Free Survival
Therapeutics
Safety
Neoplasms
Leucovorin
Liver Neoplasms
Life Expectancy
Population Groups
Fluorouracil
Multicenter Studies
Quality of Life
Research Personnel

Keywords

  • Liver metastases
  • Metastatic colorectal cancer
  • Selective Internal Radiation Therapy (SIRT)
  • SIR-Spheres® microspheres
  • Systemic chemotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

Cite this

@article{f2b657afb55a45fcb63c9bb9b562d629,
title = "Selective Internal Radiation Therapy (SIRT) with yttrium-90 resin microspheres plus standard systemic chemotherapy regimen of FOLFOX versus FOLFOX alone as first-line treatment of non-resectable liver metastases from colorectal cancer: The SIRFLOX study",
abstract = "Background: 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-Spheres{\circledR} 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-native 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. Discussion: 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. Trial registration: SIRFLOX ClinicalTrials.gov identifier: NCT00724503. Registered 25 July 2008.",
keywords = "Liver metastases, Metastatic colorectal cancer, Selective Internal Radiation Therapy (SIRT), SIR-Spheres{\circledR} microspheres, Systemic chemotherapy",
author = "{SIRFLOX Study Group} and Peter Gibbs and Val Gebski and {Van Buskirk}, Mark and Kenneth Thurston and Cade, {David N.} and {Van Hazel}, {Guy A.} and Pradip Amin and Bruna Angelelli and Jacques Balosso and Alex Beny and Daniel Bloomgarden and Eveline Boucher and Michael Brown and Bruch, {Harald Robert} and James Bui and Matthew Burge and Giuseppe Cardaci and James Carlisle and Chen, {Yi Jen} and Patrick Chevallier and Stephen Clarke and Andrew Coveler and Michel Craninx and Thierry Delanoit and Am{\'e}lie Deleporte and Paul Eliadis and Francis Facchini and Thomas Ferguson and Michel Ferrante and Michael Findlay and Gary Frenette and Jacob Frick and Vinod Ganju and Michael Garofalo and Karen Geboes and Gerald Gehbauer and Benjamin George and Ravit Geva and Michael Gordon and Seza Gulac and James Hannigan and Volker Heinemann and Thomas Helmberger and Matthew Holtzman and Richard Isaacs and Philip James and Andreas Kaubisch and Ko, {Yon Dschun} and Todd Kooy and Hendrik Kr{\"o}ning",
year = "2014",
month = "12",
day = "1",
doi = "10.1186/1471-2407-14-897",
language = "English (US)",
volume = "14",
journal = "BMC Cancer",
issn = "1471-2407",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Selective Internal Radiation Therapy (SIRT) with yttrium-90 resin microspheres plus standard systemic chemotherapy regimen of FOLFOX versus FOLFOX alone as first-line treatment of non-resectable liver metastases from colorectal cancer

T2 - The SIRFLOX study

AU - SIRFLOX Study Group

AU - Gibbs, Peter

AU - Gebski, Val

AU - Van Buskirk, Mark

AU - Thurston, Kenneth

AU - Cade, David N.

AU - Van Hazel, Guy A.

AU - Amin, Pradip

AU - Angelelli, Bruna

AU - Balosso, Jacques

AU - Beny, Alex

AU - Bloomgarden, Daniel

AU - Boucher, Eveline

AU - Brown, Michael

AU - Bruch, Harald Robert

AU - Bui, James

AU - Burge, Matthew

AU - Cardaci, Giuseppe

AU - Carlisle, James

AU - Chen, Yi Jen

AU - Chevallier, Patrick

AU - Clarke, Stephen

AU - Coveler, Andrew

AU - Craninx, Michel

AU - Delanoit, Thierry

AU - Deleporte, Amélie

AU - Eliadis, Paul

AU - Facchini, Francis

AU - Ferguson, Thomas

AU - Ferrante, Michel

AU - Findlay, Michael

AU - Frenette, Gary

AU - Frick, Jacob

AU - Ganju, Vinod

AU - Garofalo, Michael

AU - Geboes, Karen

AU - Gehbauer, Gerald

AU - George, Benjamin

AU - Geva, Ravit

AU - Gordon, Michael

AU - Gulac, Seza

AU - Hannigan, James

AU - Heinemann, Volker

AU - Helmberger, Thomas

AU - Holtzman, Matthew

AU - Isaacs, Richard

AU - James, Philip

AU - Kaubisch, Andreas

AU - Ko, Yon Dschun

AU - Kooy, Todd

AU - Kröning, Hendrik

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Background: 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-Spheres® 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-native 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. Discussion: 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. Trial registration: SIRFLOX ClinicalTrials.gov identifier: NCT00724503. Registered 25 July 2008.

AB - Background: 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-Spheres® 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-native 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. Discussion: 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. Trial registration: SIRFLOX ClinicalTrials.gov identifier: NCT00724503. Registered 25 July 2008.

KW - Liver metastases

KW - Metastatic colorectal cancer

KW - Selective Internal Radiation Therapy (SIRT)

KW - SIR-Spheres® microspheres

KW - Systemic chemotherapy

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U2 - 10.1186/1471-2407-14-897

DO - 10.1186/1471-2407-14-897

M3 - Article

VL - 14

JO - BMC Cancer

JF - BMC Cancer

SN - 1471-2407

IS - 1

M1 - 897

ER -