Table 1. Systemic therapies and their potential toxicities when combined with SIRT.
| Drug name | Potential effects when combined with SIRT | References/ongoing studies, NCTa ID | Recommendation | |
|---|---|---|---|---|
| Synergy | Toxicity | |||
| Chemotherapy agents | ||||
| 5FU | Radiosensitization | Liver toxicity | Hendlisz et al. 2010 (14)/– | No safety concerns |
| Capecitabine | Radiosensitization | Liver toxicity | Cohen et al. 2014 (26)/– | Capecitabine 1,000 mg/m2 bid is recommended for phase II study |
| Oxaliplatin, platinum | Radiosensitization | Liver toxicity | Sharma et al. 2007 (18)/NCT02807181 | Reduced dose as used in SIRFLOX |
| Irinotecan | Radiosensitization | Liver toxicity | Gulec et al. 2014 (27), van Hazel et al. 2009 (16)/– | Irinotecan 100 mg/m2 on days 1 and 8 of a 3-week cycle is recommended |
| TAS 102 | Radiosensitization | Liver toxicity | –/NCT02602327 | SCTb |
| Taxanes | Radiosensitization | Unknown | Unknown | Unknown |
| Gemcitabine | Radiosensitization | Unknown | Iñarrairaegui et al. 2015 (28)/NCT02807181 | SCT |
| Octreotide | Radiosensitization | None | Kennedy et al. 2015 (29)/– | No safety concerns |
| Lanreotide | Radiosensitization | None | –/NCT02859064 | SCT |
| Temozolomide | Radiosensitization | Unknown | Unknown | Unknown |
| Inhibitors of tumor signalling pathways | ||||
| Sunitinib | Increased dose delivered to healthy liver due to reduced tumor arterial blood flow and increased risk of GI hemorrhage | –/– | – | |
| Sorafenib | Increased dose delivered to healthy liver due to reduced tumor arterial blood flow and increased risk of GI hemorrhage | Salman et al. 2016 (30)/NCT01126645 | No apparent safety concerns with regular dose | |
| Regorafenib | Increased dose delivered to healthy liver due to reduced tumor arterial blood flow and increased risk of GI hemorrhage | Kennedy et al. 2017 (31)/– | Preliminary results show no safety concerns with sequential use | |
| Bevacizumab | Increased dose delivered to healthy liver due to reduced tumor arterial blood flow and increased risk of GI hemorrhage | van Hazel et al. 2016 (7)/– | No apparent safety concerns with regular dose | |
| Trastuzumab | Liver toxicity | –/– | – | |
| Immune checkpoint inhibitors/cell-based immunotherapy | ||||
| Ipilimumab, tremelimumab (anti-CTLA-4) | Release of tumor-specific T cell response | Liver-directed autoimmunity | NA/NCT02913417; NCT03005002 | SCT |
| Nivolumab, pembrolizumab (anti-PD1) | Release of tumor-specific T cell response | Liver-directed autoimmunity | NA/NCT03033446; NCT02913417 | SCT |
| Atezolizumab, durvalumab (anti-PDL1) | Release of tumor-specific T cell response | Liver-directed autoimmunity | NA/NCT03005002 | SCT |
| CARc T cells | Redirection of T cell effector functions | CRSd-induced hepatotoxicity | NA/NCT02416466 | SCT |
a, National Clinical Trial; b, Subject to Clinical Trial; c, chimeric antigen receptor; d, cytokine release syndrome. SIRT, selective internal radiation therapy; GI, gastrointestinal; NA, not available/applicable; 5Fu, 5-fluorouracil; CRC, colorectal cancer.