SIRFLOX: Randomized Phase III Trial Comparing First-Line mFOLFOX6 (Plus or Minus Bevacizumab) Versus mFOLFOX6 (Plus or Minus Bevacizumab) Plus Selective Internal Radiation Therapy in Patients With Metastatic Colorectal Cancer.

SIRFLOX was a randomized, multicenter trial designed to assess the efficacy and safety of adding selective internal radiation therapy (SIRT) using yttrium-90 resin microspheres to standard fluorouracil, leucovorin, and oxaliplatin (FOLFOX)-based chemotherapy in patients with previously untreated metastatic colorectal cancer.

Chemotherapy-naïve patients with liver metastases plus or minus limited extrahepatic metastases were randomly assigned to receive either modified FOLFOX (mFOLFOX6; control) or mFOLFOX6 plus SIRT (SIRT) plus or minus bevacizumab. The primary end point was progression-free survival (PFS) at any site as assessed by independent centralized radiology review blinded to study arm.

Between October 2006 and April 2013, 530 patients were randomly assigned to treatment (control, 263; SIRT, 267). Median PFS at any site was 10.2 v 10.7 months in control versus SIRT (hazard ratio, 0.93; 95% CI, 0.77 to 1.12; P = .43). Median PFS in the liver by competing risk analysis was 12.6 v 20.5 months in control versus SIRT (hazard ratio, 0.69; 95% CI, 0.55 to 0.90; P = .002). Objective response rates (ORRs) at any site were similar (68.1% v 76.4% in control v SIRT; P = .113). ORR in the liver was improved with the addition of SIRT (68.8% v 78.7% in control v SIRT; P = .042). Grade ≥ 3 adverse events, including recognized SIRT-related effects, were reported in 73.4% and 85.4% of patients in control versus SIRT.

The addition of SIRT to FOLFOX-based first-line chemotherapy in patients with liver-dominant or liver-only metastatic colorectal cancer did not improve PFS at any site but significantly delayed disease progression in the liver. The safety profile was as expected and was consistent with previous studies.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2016 Feb 22 [Epub]

Guy A van Hazel, Volker Heinemann, Navesh K Sharma, Michael P N Findlay, Jens Ricke, Marc Peeters, David Perez, Bridget A Robinson, Andrew H Strickland, Tom Ferguson, Javier Rodríguez, Hendrik Kröning, Ido Wolf, Vinod Ganju, Euan Walpole, Eveline Boucher, Thomas Tichler, Einat Shacham-Shmueli, Alex Powell, Paul Eliadis, Richard Isaacs, David Price, Fred Moeslein, Julien Taieb, Geoff Bower, Val Gebski, Mark Van Buskirk, David N Cade, Kenneth Thurston, Peter Gibbs

Guy A. van Hazel, University of Western Australia; Tom Ferguson, Royal Perth Hospital; David Price and Geoff Bower, Mount Medical Center, Perth; Alex Powell, Hollywood Private Hospital, Nedlands, Western Australia; Andrew H. Strickland, Monash Medical Centre, Bentleigh, East Victoria; Vinod Ganju, Frankston Private Hospital Peninsula Oncology Centre, Frankston; Peter Gibbs, Western Hospital, Footscray, Victoria; Euan Walpole, Princess Alexandra Hospital, Woolloongabba; Paul Eliadis, Wesley Medical Centre, Milton, Queensland; Val Gebski, NHMRC Clinical Trials Centre, Camperdown; David N. Cade and Kenneth Thurston, Sirtex Medical Limited, North Sydney, New South Wales, Australia; Volker Heinemann, Ludwig-Maximilian-University of Munich, Munich; Jens Ricke, University Clinic Magdeburg; Hendrik Kroening, Schwerpunktpraxis of Haematology and Oncology, Magdeburg, Germany; Navesh K. Sharma, University of Maryland Medical Center; Fred Moeslein, University of Maryland School of Medicine, Baltimore, MD; Mark Van Buskirk, Data Reduction LLC, Chester, NJ; Michael P.N. Findlay, Cancer Trials New Zealand, Auckland; David Perez, Dunedin Hospital, Dunedin; Bridget A. Robinson, Christchurch Hospital, Christchurch; Richard Isaacs, Palmerston North Hospital, Palmerston, New Zealand; Marc Peeters, Antwerp University Hospital, Antwerp, Belgium; Javier Rodríguez, Clinica Universidad de Navarra, Pamplona, Spain; Ido Wolf and Einat Shacham-Shmueli, Sheba Medical Center, Tel-Hashomer; Thomas Tichler, Shaare-Zedek Medical Center, Jerusalem, Israel; Eveline Boucher, Hopital de Jour, Rennes; and Julien Taieb, Georges Pompidou European Hospital, Paris, France. This email address is being protected from spambots. You need JavaScript enabled to view it.., Guy A. van Hazel, University of Western Australia; Tom Ferguson, Royal Perth Hospital; David Price and Geoff Bower, Mount Medical Center, Perth; Alex Powell, Hollywood Private Hospital, Nedlands, Western Australia; Andrew H. Strickland, Monash Medical Centre, Bentleigh, East Victoria; Vinod Ganju, Frankston Private Hospital Peninsula Oncology Centre, Frankston; Peter Gibbs, Western Hospital, Footscray, Victoria; Euan Walpole, Princess Alexandra Hospital, Woolloongabba; Paul Eliadis, Wesley Medical Centre, Milton, Queensland; Val Gebski, NHMRC Clinical Trials Centre, Camperdown; David N. Cade and Kenneth Thurston, Sirtex Medical Limited, North Sydney, New South Wales, Australia; Volker Heinemann, Ludwig-Maximilian-University of Munich, Munich; Jens Ricke, University Clinic Magdeburg; Hendrik Kroening, Schwerpunktpraxis of Haematology and Oncology, Magdeburg, Germany; Navesh K. Sharma, University of Maryland Medical Center; Fred Moeslein, University of Maryland School of Medicine, Baltimore, MD; Mark Van Buskirk, Data Reduction LLC, Chester, NJ; Michael P.N. Findlay, Cancer Trials New Zealand, Auckland; David Perez, Dunedin Hospital, Dunedin; Bridget A. Robinson, Christchurch Hospital, Christchurch; Richard Isaacs, Palmerston North Hospital, Palmerston, New Zealand; Marc Peeters, Antwerp University Hospital, Antwerp, Belgium; Javier Rodríguez, Clinica Universidad de Navarra, Pamplona, Spain; Ido Wolf and Einat Shacham-Shmueli, Sheba Medical Center, Tel-Hashomer; Thomas Tichler, Shaare-Zedek Medical Center, Jerusalem, Israel; Eveline Boucher, Hopital de Jour, Rennes; and Julien Taieb, Georges Pompidou European Hospital, Paris, France.

Go beyond the abstract: Read an original commentary by the authors