Table 1.

Results of published case reports and clinical trials for TKI usage in CCA

Drug	Number of patients	Dose	Duration of treatment	Outcome	Side effects	Refs.
Sorafenib	2	400 mg PO bid	4 months with later switch to oxaliplatin and gemcitabine; 6 month for the time of report	Transient disease stabilization; decrease of tumor markers CA 125, CA 19-9, CA 27.29	Maculopapular rash, hair thinning, grade 3 thrombocytopenia (disappeared after 1-week discontinuation), hypertension, facial rush	[13]
Sorafenib	1	400 mg PO bid	2 years for the time of report	Stable disease with time-to-progression 5.7 month; decrease of tumor marker CA 19-9; decrease of bilirubin level and increase of liver synthesis parameters	Mild diarrhea, fatigue and skin toxicity; no dose reduction or interruption were made	[12]
Sorafenib	1	400 mg PO bid; 7 days cessation after 1 year and dose reduction to 200 mg	4 years for the time of report	Stable disease; decrease of bilirubin level	Mild diarrhea, desquamation rush. Grade 1 hand-foot syndrome, mild thrombocytopenia (required 7 days cessation)	[11]
Sorafenib	44	400 mg PO bid	1.8-month median duration	Median time to progression 5.6 month; median overall survival 5.7 month; disease control rate at 3 months 15.9%	Mild diarrhea, fatigue, hand-foot syndrome	[14]
Sorafenib	15	400 mg PO bid	3.2-month median duration	Median time to progression 3.2 month; median overall survival 5.7 month; disease control rate at 3 months 73.3%	Skin rush in 5 patients grade 3 hand-foot syndrome in 1 patient	[15]
Sorafenib	31	400 mg PO bid	2-month median duration	Disease control rate detected according suggested scheme 0%; median overall survival 9 month; median progression free survival 3 month	Grades 3 and 4 toxicities in 20 patients included: thrombosis/embolism, hypertension, fatigue, bilirubin evaluation, hand-foot syndrome	[16]
Sorafenib	46	400 mg PO bid	From 1 to 12 months	Disease control rate at 3 months 32.6%; median overall survival 4.4 month; median progression free survival 2.3 month	Hand-foot syndrome, skin rush, diarrhea, fatigue and thrombocytopenia	[17]
Pazopanib Trametinib	25	Pazopanib 800 mg qd Trametinib 2 mg qd	3-month median duration	Median overall survival 6.4 month; disease control rate detected according suggested scheme 75%; median progression free survival 3.6 month	Hypertension, fatigue, rash, diarrhea, nausea/vomiting, thrombocytopenia	[18]