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Updated: May 23, 2026
Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver
Published on: July 31, 2016
Phase II study of sirolimus in treatment-naive patients with advanced hepatocellular carcinoma
Thomas Decaens1, Alain Luciani, Emmanuel Itti
1AP-HP, Groupe hospitalier Henri Mondor, Department of Hepatology, Creteil, France. thomas.decaens@hmn.aphp.fr
Background:
Rapalogs are emerging as promising targeted anticancer drugs. Activation of the PI3K/Akt/mTOR pathway has been observed in 15-50% of hepatocellular carcinomas.
Methods:
In this phase II study, patients with advanced hepatocellular carcinoma and underlying cirrhosis received sirolimus (20 mg/week for 1 month then 30 mg/week). Tumour response was assessed every 8 weeks. The primary endpoint was the objective tumour response rate according to the Response Evaluation Criteria in Solid Tumours criteria. Secondary endpoints included the objective response according to the modified Response Evaluation Criteria in Solid Tumours criteria, safety, and pharmacokinetic parameters.
Results:
Twenty-five patients received sirolimus for a median of 20.6 weeks. Two patients had an objective response (8%, 95CI: 0.98-26.03), including one complete response, and 8 patients had stable disease. There were 2 cases of grade 5 toxicity (infections) and 5 cases of grade 3 toxicity. The main grade 1/2 toxicity was mild transient fatigue (76%). Median time to radiological progression and overall survival were 15.3 weeks (range: 8.2-173.9) and 26.4 weeks (range: 8.2-173.9) respectively. Use of the modified Response Evaluation Criteria in Solid Tumours criteria did not identify any further responders.
Conclusion:
These data suggest that first-line sirolimus shows antitumoural efficacy in advanced hepatocellular carcinoma. Larger trials with Child A patients are needed.
Insights
First-line sirolimus demonstrated anticancer effects in advanced hepatocellular carcinoma patients. Further research in Child A patients is recommended to confirm efficacy and safety.
Area of Science:
- Oncology
- Pharmacology
Background:
- Rapalogs are emerging targeted anticancer drugs.
- The PI3K/Akt/mTOR pathway is activated in 15-50% of hepatocellular carcinomas (HCC).
Purpose of the Study:
- To evaluate the efficacy and safety of sirolimus as a first-line treatment for advanced HCC.
Main Methods:
- A phase II study involving 25 patients with advanced HCC and cirrhosis receiving sirolimus.
- Tumor response assessed using Response Evaluation Criteria in Solid Tumours (RECIST) criteria.
- Safety and pharmacokinetic parameters were secondary endpoints.
Main Results:
- Sirolimus showed an 8% objective response rate (ORR), with one complete response and stable disease in 8 patients.
- Median time to progression was 15.3 weeks, and median overall survival was 26.4 weeks.
- Grade 5 toxicity (infections) occurred in 2 patients; grade 3 toxicity in 5 patients. Fatigue was the most common toxicity.
Conclusions:
- First-line sirolimus exhibits antitumoral efficacy in advanced HCC.
- Larger clinical trials focusing on Child A patients are necessary.
