A randomised phase II/III trial of 3-weekly cisplatin-based sequential transarterial chemoembolisation vs embolisation alone for hepatocellular carcinoma

Background: Transarterial chemoembolisation (TACE) has not been shown to be superior to bland embolisation (TAE) for treatment of hepatocellular carcinoma (HCC). Methods: We conducted a randomised phase II/III trial in patients with untreated HCC. Patients were randomised to TAE with polyvinyl alcohol (PVA) particles alone or sequential TACE (sTACE) in which cisplatin 50 mg was administered intrarterially 4-6 h before PVA embolisation. Treatment was repeated 3-weekly for up to three treatments. The primary endpoint was overall survival and secondary endpoints were progression-free survival, toxicity and response. Target sample sizes for phase II and III were 80 and 322. Results: The trial was terminated at phase II after 86 patients had been randomised. Patients were well matched for prognostic criteria. All three planned treatments were given to 57.1% (TAE) and 56.8% (TACE) patients. Grade 3/4 toxicity occurred in 63.5% and 83.7%, respectively (P = 0.019). End-of-treatment RECIST response (CR_PR) was 13.2 and 32.6% (P = 0.04) (mRECIST 47.3% and 67.4) and median overall survival and progression-free survival was 17.3 vs 16.3 (P = 0.74) months and 7.2 vs 7.5 (P = 0.59), respectively. Conclusion: Transarterial chemoembolisation according this novel schedule is feasible and associated with a higher response rate than TAE alone. The survival benefit of TACE over TAE remains unproven.