Efficacy of Sirolimus In Liver Transplantation for Hepatocellular Carcinoma (HCC)
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to evaluate the anti-tumor effect of sirolimus-based
      immunosuppressive regimen in patients following living donor liver transplantation for
      hepatocellular carcinoma exceeding Milan criteria with respect to recurrence-free survival.
    

Detailed description: 
      The Milan criteria were adopted in most of western countries for deceased donor allocation
      because they identify a subgroup of candidates with hepatocellular carcinoma (HCC) for whom
      transplant results are similar to those in patients transplanted for end- stage liver disease
      without HCC. There is a debate involving expanding the indications beyond the Milan criteria
      in living donor liver transplantation (LDLT). Some transplant surgeons argue that despite the
      poorer results, LDLT for advanced HCC may be justified, since donors voluntarily accept the
      risks of donor hepatectomy to dedicate a graft for HCC patients, who may otherwise have no
      effective treatment. Especially, in Korea where living donor liver transplantation (LDLT) is
      commonly performed, the expansion of Milan criteria is inevitable. Sirolimus is a macrolide
      antibiotic produced by Streptomyces hygroscopic that has demonstrated potent
      immunosuppressive activity in a number of studies. The efficacy of sirolimus as
      immunosuppressives has been demonstrated in randomized clinical trials in kidney
      transplantation. The use of sirolimus in liver transplantation is rapidly increasing from the
      standpoint of reducing the conventional calcineurin inhibitor toxicity. Sirolimus emerged as
      an effective alternative for patients with renal insufficiency related to calcineurin
      inhibitor toxicity. In recent studies, no differences have been observed with respect to
      rejection or major complications.The use of sirolimus in transplant patients is associated
      with a dose-dependent increase in serum cholesterol and triglycerides that may require
      treatment. In recent studies in liver transplant recipients using sirolimus as part of a
      primary immunosuppressive regimen, the occurrence of acute cellular rejection is relatively
      low. There is data suggesting that sirolimus is associated with hepatic artery thrombosis.
      Numerous current studies have shown that sirolimus may have inhibitory effects on the
      development of cancer. Immunosuppressive agent with antineoplastic activity is inherently
      attractive in the setting of liver transplantation for HCC. If sirolimus shows some degree of
      anti-tumor effect in transplant recipients with advanced HCC, the indication of LDLT for
      advanced HCC can be expanded.Our hypothesis is that sirolimus based-regimen will improve the
      HCC recurrence free survival. If sirolimus-based protocol shows better recurrence free
      survival, the indication of LDLT for HCC can be expanded. LDLT can be one of the best
      treatment modalities for advanced HCC. The patients with advanced HCC can have benefit by
      liver transplantation.
    

Intervention name(s): Sirolimus; m-TOR inhibitor free
Intervention type(s): Drug; Drug
Intervention description(s): Sirolimus; calcineurin inhibitors
Other intervention name(s): Rapamune; Tacrolimus; Cyclosporine
Intervention MeSH terms: Cyclosporine; Sirolimus; Tacrolimus; Cyclosporins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment