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] |