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Abstract
BackgroundTransarterial chemoembolization (TACE) and sorafenib are the therapeutic standard for intermediate and advanced stage hepatocellular carcinoma (HCC) patients respectively. High costs with adverse events (AE) of sorafenib might limit sorafenib dosage, further affecting therapeutic response. To attain greatest benefit, we evaluated the efficacy of different doses and effect of TACE during and after sorafenib discontinuation in patients representing Child-Pugh Classification Class A with venous or extra-hepatic invasion.MethodsA total 156 patients met the criteria and were divided into Groups I (n = 52) accepting 800 mg/day; II (n = 58) accepting 800 mg/day and reduced to 400 mg/day owing to AE; and III (n = 46) accepting 400 mg/day. TACE was performed during and after sorafenib discontinuation and therapeutic response bimonthly to four-monthly was rated thereafter.ResultsMedian duration of sorafenib treatment and patients’ survival were 4.00 ± 0.45 and 7.50 ± 1.44 months in all cases; 2.50 ± 0.90 and 5.00 ± 1.10 months in Group I; 5.50 ± 1.27 and 16.50 ± 1.86 months in Group II; 4.00 ± 0.94 and 6.50 ± 2.49 months in Group III. Group II presented the best response and survival benefit (p = 0.010 and p = 0.011 respectively). Child-Pugh Classification score 5 (Hazard Ratio = 0.492, p = 0.049), absent AE (3.423, p = 0.015), tumor numbers ≤ 3 (0.313, p = 0.009), sorafenib duration ≤ 1 cycle (3.694, p = 0.004), and absent TACE (3.197, p = 0.008) significantly correlated with patient survival. TACE benefit appeared in separate and total cases during (p = 0.002, p = 0.595, p = 0.074, p = 0.002 respectively) and after discontinuation of sorafenib administration (p = 0.001, p = 0.034, p = 0.647, p = 0.001 respectively).ConclusionsLow-dosage sorafenib not only appeared tolerable and lowered economic pressure but also provided satisfactory results. TACE benefited patient’s survival during and after sorafenib discontinuation.
Highlights
Transarterial chemoembolization (TACE) and sorafenib are the therapeutic standard for intermediate and advanced stage hepatocellular carcinoma (HCC) patients respectively
Anti-angiogenic function is via inhibition of VEGFR2-PDGFR- and Raf-kinase properties [5,6,7], signaling pathways identified as a close rationale in HCC study and providing survival benefits in advanced HCC [Barcelona Clinic Liver Cancer (BCLC) stage C] [7,8,9,10,11,12]
We found despite Groups II and III presenting poorer baseline characteristics than I including lower albumin (3.68 ± 0.51 g/dL versus 4.05 ± 0.42 g/dL, p < 0.001 respectively) and older age (64.5 ± 12.02 versus 58.75 ± 13.33 years, p = 0.028 respectively) (Table 1), Groups II and III rather than I still showed better sorafenib response and survival benefit (p = 0.010 and p = 0.011 respectively) (Fig. 2) as our finding of poorer sorafenib response significantly correlated with higher mortality (r = 0.756, p < 0.001)
Summary
Transarterial chemoembolization (TACE) and sorafenib are the therapeutic standard for intermediate and advanced stage hepatocellular carcinoma (HCC) patients respectively. Limitations affect patients treated with sorafenib in clinical scenarios: e.g., high cost raising economic pressure [13], while severe adverse events (AE) (26–88 %) might limit sorafenib dosage and impair therapeutic response, as well as high tumor recurrence with single agent [8, 9, 14, 15]. Transarterial chemoembolization (TACE) is the current standard therapy for intermediate stage HCC (BCLC stage B) and an earlier study indicated combination of TACE with sorafenib as being more effective than TACE or sorafenib monotherapy for unresectable HCC [17]; but no data is reported on the exploration of the effect of different sorafenib dosage with subsequent TACE during or after discontinued sorafenib
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