Chemotherapy Plus Radiation Demonstrated Control of Liver Metastases in Colon Cancer Interview with:

Dr Guy van Hazel Clinical Professor of Medicine, School of Medicine and Pharmacology, University of Western Australia

Dr. Guy van Hazel

Dr Guy van Hazel
Clinical Professor of Medicine,
School of Medicine and Pharmacology,
University of Western Australia 

Medical Research: What is the background for this study? What are the main findings?

Dr. van Hazel: The SIRFLOX study is based on original work by Dr Bruce Gray and myself almost two decades ago, when we studied the combination of Selective Internal Radiation Therapy (SIRT) with Y-90 resin microspheres – which was absolutely new at the time – with hepatic artery chemotherapy. This study showed an increase in liver control with the addition of SIRT [Gray B et al. Ann Oncol 2001; 12: 1711–1720.].

We then proceeded to initiate a trial comparing systemic SIRT plus 5-FU/LV according to the Mayo Clinic regimen compared to the Mayo Clinic regimen alone, but unfortunately this had to be abandoned because new chemotherapy became available which made it unethical to offer the control arm. However, in those patients who were treated up to that point with SIRT plus 5-FU/LV [van Hazel G et al. J Surg Oncol 2004; 88: 78–85.] we did see a very high response rates compared to the control arm, with an impressive survival of 29 months. We subsequently did a phase l/ll study of modified FOLFOX6 with or without SIRT and again found very high response rates [Sharma R et al. J Clin Oncol 2007; 25: 1099–1106.].  This led us to launch the SIRFLOX study in 2007.

Medical Research: What should clinicians and patients take away from your report?

Dr. van Hazel: I think physicians should take away the fact that we demonstrated very good control of liver metastases with the addition of SIRT with Y-90 resin microspheres to mFOLFOX6 with or without bevacizumab in the first-line treatment of unresectable metastatic colo-rectal cancer, and that the use of this treatment may eventually translate into a survival benefit. Physicians should also be comforted by the relatively low toxicity that accompanied the use of SIRT in these patients.

The survival question should be answered when we get the results of the combined analysis of the SIRFOX, FOXFIRE and FOXFIRE Global studies, which will comprise more than 1100 patients, and should be available in 2017.

It is unfortunate that we did not get a positive overall progression-free survival (PFS) signal from the SIRFLOX study itself, which may have been because we accepted patients with low volume extra hepatic disease and patients with intact primaries.  SIRT works only in the liver, and thus cannot be expected to have any impact on extrahepatic disease.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. van Hazel: I think we should probably investigate a tighter defined group of colo-rectal cancer patients with hepatic only metastases. We also are exploring an extensive list of additional analyses of the SIRFLOX study, looking at age, bulk of disease, depth of response and many other variables to see how they impacted on the outcome of the treatment. 

Medical Research: Is there anything else you would like to add?

Dr. van Hazel: For me, the bottom line, is that SIRFLOX shows us, in a substantial patient cohort, that loco-regional treatment of mCRC has a role to play in the management of this disease alongside available chemotherapeutic and biological options.  SIRT is the first type of radiological treatment that enables us to deliver sufficiently high doses of radiation to liver tumours while sparing healthy liver tissue. The results of the SIRFLOX study are important as the liver is the most common site of colorectal cancer metastases. These tumours contribute significantly to liver failure, which is the most frequent cause of patient deaths.


J Clin Oncol. 2016 Feb 22. pii: JCO661181. [Epub ahead of print]

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.

van Hazel GA1, Heinemann V2, Sharma NK2, Findlay MP2, Ricke J2, Peeters M2, Perez D2, Robinson BA2, Strickland AH2, Ferguson T2, Rodrigez J2, Kröning H2, Wolf I2, Ganju V2, Walpole E2, Boucher E2, Tichler T2, Shacham-Shmueli E2, Powell A2, Eliadis P2, Isaacs R2, Price D2, Moeslein F2, Taieb J2, Bower G2,Gebski V2, Van Buskirk M2, Cade DN2, Thurston K2, Gibbs P2.

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Dr Guy van Hazel (2016). Chemotherapy Plus Radiation Demonstrated Control of Liver Metastases in Colon Cancer