Adjuvant celecoxib and lanreotide following transarterial chemoembolisation for unresectable hepatocellular carcinoma: a randomized pilot study

Abstract

Recurrence of hepatocellular carcinoma (HCC) after transarterial chemoembolisation (TACE) is common due to neoangiogenesis. Cyclooxygenase-2 inhibitors and somatostatin analogues were reported to inhibit tumour angiogenesis. The pilot randomized controlled trial was aimed to prospectively evaluate the protocol of TACE combined with celecoxib and lanreotide (TACE+C+L) in patients with unresectable and advanced HCC. A total of 71 patients with HCC were enrolled and randomly assigned to either TACE (n=35) or TACE+C+L (n=36) group. Overall survival, disease control rate (DCR), and adverse events were assessed during a 3-year follow-up period. The median overall survival of the TACE+C+L group (15.0 months) was doubled compared to that of TACE group (7.5 months), p = 0.012. DCR of the TACE+C+L group was significantly higher than that of the TACE group either at 6 months (72.2% vs 42.9%, p = 0.012) or at 12 months (61.1% vs 28.6%, p = 0.006). The median overall survivals (13 months vs 4.5 months, p = 0.013) and DCR at 12 months (50% vs 13.6%, p = 0.008) of patients with advanced HCC in TACE+C+L groups were significantly higher than those in TACE group. No significant difference of adverse events was observed between the two groups. The occurrence of post-embolisation syndrome in TACE+C+L group was significantly lower than that in TACE group (16.7% vs 60.0%, p = 0.001). In conclusion, the regimen of TACE+C+L prolonged overall survival, enhanced tumour response, reduced post-embolisation syndrome and was well-tolerable in the patients with unresectable HCC. It may be more beneficial for advanced HCC.

<p>Suppressing growth and invasion of human hepatocellular carcinoma cells by celecoxib through inhibition of cyclooxygenase-2</p>

“…Based on the inflammation-fibrosis-cancer axis, the anti-fibrotic effects of celecoxib make it a novel non-cytotoxic drug candidate in the prevention and treatment of HCC. More recently, a randomized clinical trial has shown that adjuvant celecoxib following transarterial chemoembolization enhanced tumor response and prolonged overall survival in unresectable HCC patients 20. Therefore, the anti-tumor effect and mechanism of celecoxib against HCC deserves further investigation.…”

Role of locoregional therapies in the wake of systemic therapy

“…In a prospective randomised study of 71 patients, Tong et al compared TACE alone or combined with the selective COX-2 inhibitor, celecoxib and the somatostatin analogue, lanreotide in advanced HCC. 50 The patients receiving the combination treatment had a median OS of 15 months compared to 7.5 months for those receiving TACE alone, and a subgroup analysis of advanced patients demonstrated an OS of 13 months for the combination and 4.5 months for TACE alone (p = 0.013). Disease control at 12 months was 72.2% and 42.9% for combined treatment vs. TACE alone (p = 0.008), with no significant differences in AEs except for post embolisation syndrome, which occurred less frequently in the combination arm (16.5% vs. 60%; p = 0.001).…”

The Role of Angiogenesis in Hepatocellular Carcinoma

“…New agents or combinations of synergizing agents with differing or broader selectivity to inhibit a variety of angiogenic pathways, or targeting agents to specific populations with a sensitizing mutation may potentially overcome initial or acquired resistance to initial antiangiogenic inhibitor treatment. Some agents are already demonstrating encouraging results in the laboratory and clinic (13,36,43,(77)(78)(79).…”