Abstract
BackgroundIn 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/DesignSIRFLOX 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-naïve 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.DiscussionThe 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 registrationSIRFLOX ClinicalTrials.gov identifier: NCT00724503. Registered 25 July 2008.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-897) contains supplementary material, which is available to authorized users.
Highlights
In colorectal cancer (CRC), unresectable liver metastases are linked to poor prognosis
The SIRFLOX trial will establish the potential role of Selective Internal Radiation Therapy (SIRT) + standard systemic chemotherapy in the first-line management of metastatic CRC (mCRC) with non-resectable liver metastases
These results suggest that the combination of SIRT and FOLFOX systemic chemotherapy warrants further investigation
Summary
The SIRFLOX study will assess the efficacy and safety of SIRT in combination with FOLFOX-based systemic chemotherapy as first-line treatment of patients with inoperable liver-only or liver-predominant mCRC. Previous trials have shown that first-line SIR-Spheres plus chemotherapy can significantly increase time-to-progression and survival in patients with mCRC [22,24], these used chemotherapy regimens that are outdated in the management of mCRC This provides the rationale for choosing mFOLFOX6 in the study. The approach of combining systemic chemotherapy ± biologic agents with targeted radiation therapy may provide enhanced benefits in mCRC Another strata that will be assessed in these trials is the absence or presence of extra-hepatic metastases. In addition to the SIRFLOX study, SIRT in combination with FOLFOX-based systemic chemotherapy as first-line treatment of patients with inoperable liver-only or liver-predominant mCRC is being investigated in the FOXFIRE trial. All authors were involved in drafting or critically reviewing each draft of the manuscript for important intellectual content, and all authors read and approved the final draft of the manuscript for submission
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