Review
Copyright ©2013 Baishideng Publishing Group Co.
World J Hepatol. Jul 27, 2013; 5(7): 345-352
Published online Jul 27, 2013. doi: 10.4254/wjh.v5.i7.345
Table 1 Completed clinical trials for overcoming sorafenib resistance
Therapeutic strategiesPhasesCasesEfficacy
Combinational therapy
5-fluorouracil plus sorafenib[46]Phase II39SD: 46.2%; median TTP: 8 mo; OS: 13.7 mo
Tegafur/uracil plus sorafenib[47]Phase II53Median PFS: 3.7 mo; median OS: 7.4 mo
Octreotide plus sorafenib[48]Phase II (So.LAR.)50SD: 66%; median TTP: 7.0 mo; median OS: 12 mo
Doxorubicin plus sorafenib vs doxorubicin plus placebo[50]Phase III47 vs 49Median TTP: 6.4 mo vs 2.8 mo; OS: 13.7 mo vs 6.5 mo; PFS: 6.0 mo vs 2.7 mo
Erlotinib plus sorafenib vs erlotinib plus placebo[53,54]Phase III (SEARCH)362Median TTP: 3.2 mo vs 4.0 mo; OS: 9.5 mo vs 8.5 mo
Second-line treatments
Sunitinib[55]Retrospective analysis11SD: 40%; median TTP: 3.2 mo
Brivanib[56]Phase II46SD: 41.3%; RR: 4.3%; DCR: 45.7%; median OS: 9.79 mo
Tivantinib vs placebo[6]Phase II71 vs 36Progressive disease: 65% vs 72%; TTP: 1.6 mo vs 1.4 mo
Gemcitabine plus oxaliplatin[59]Retrospective analysis18Overall RR: 18.8%; SD: 18.8%; median PFS: 3.2 mo; OS: 4.7 mo
Erlotinib plus bevacizumab[61]Phase II10No response or SD; median TTP: 1.81 mo; OS: 4.37 mo
Table 2 Ongoing clinical trials for overcoming sorafenib resistance
StudiesTherapeutic strategiesPhasesPrimary outcomes
Combinational therapy
NCT01271504E7050 plus sorafenib vs sorafenibPhase IIAdverse event
NCT01033240CS-1008 plus sorafenib vs sorafenibPhase IITTP
NCT01539018Tegafur-uracil plus sorafenib vs sorafenibPhase IITTP
NCT01272557Doxorubicin plus sorafenib vs sorafenibPhase IITTP
NCT01015833Doxorubicin plus sorafenib vs sorafenibPhase IIIOS
NCT01214343Cisplatin/fluorouracil plus sorafenib vs sorafenibPhase IIIOS
Second-line treatments
NCT01507168GC33 vs placeboPhase IIPFS
NCT01273662AxitinibPhase IISD
NCT00717756LenalidomidePhase IIRR
NCT01545804LenalidomidePhase IISD
NCT01567930TemsirolimusPhase IIDisease progression
NCT01180959Erlotinib plus bevacizumabPhase IIPFS
NCT01140347Ramucirumabplus BSC vs placebo plus BSCPhase IIIPFS
NCT01108705Brivanib plus BSC vs placebo plus BSCPhase IIIOS
NCT00825955Brivanib plus BSC vs placebo plus BSCPhase IIIOS
NCT01035229Everolimus plus BSC vs placebo plus BSCPhase IIIOS