Sorafenib in hepatocellular carcinoma (HCC) patients after liver transplantation

Abstract

e15579 Background: Sorafenib has been approved for the treatment of advanced HCC. However, there is no data on its use for HCC patients (pts) after liver transplantation (OLT). Pts at high risk for tumor recurrence (native liver showing vascular invasion, multiple tumors >3 in number, size >6 cm, or lymph node involved) after OLT or who develop recurrence after OLT have worse prognosis. These pts may potentially benefit from sorafenib. Methods: We reviewed our experience with HCC pts after OLT treated with sorafenib. 15 pts had a starting dose of 400 mg po bid and 3 had a starting dose of 200 po bid. Sorafenib was started 3 months (mo) after OLT as adjuvant therapy (7 pts) or at the time of tumor recurrence after OLT (11 pts). CT or MRI scans of the chest/abdomen and physical exams were performed every 2–3 mo. Lab tests including serum AFP were performed monthly. Results: Median age was 60 (range 53–75). Median performance status was 90%(range 80–100). In terms of toxicity, 4 of the 15(27%) pts on the initial dose of 400 mg bid stopped sorafenib due to unacceptable toxicity and 5 (33%) had dose reduction due to toxicity. Grade 3/4 toxicity included skin rash, fatigue and anorexia, hyperbilirubinemia, chest/abdominal pain. Only 40% could continue at the full recommended starting dose of sorafenib.For the 11 pts with recurrent disease after OLT treated with sorafenib, the sites of evaluable disease include liver (5 pts), lung (3), others (3). One pt (9%) had a partial response in lung metastases for 10 mo. and the median time to tumor progression (TTP) was 4 mo. (range 2–10 mo). For pts on adjuvant sorafenib after OLT, no pt has relapsed so far with a median followup of 6+ mo. (range 2+ to 15+ mo). Conclusions: The response rate and TTP for pts treated with sorafenib for recurrent HCC after OLT is similar to HCC pts without OLT (Llovet, NEJM 2008). Since the majority of HCC pts after OLT treated with sorafenib required either dose reduction or stoppage due to toxicity which is higher than previously reported, a lower starting dose with dose escalation may be preferred. Contributing factors for toxicity may include the anti-rejection drugs (tacrolimus, mycophenolate, steroids) used for OLT which might affect pharmacokinetics(PK) of sorafenib. Further PK studies with sorafenib in HCC pts after OLT for future clinical trials are indicated. No significant financial relationships to disclose.