Metronomic capecitabine as second-line treatment for patients with hepatocellular carcinoma with preserved liver function: A phase II study.

Background: The antiangiogenic drug sorafenib is standard treatment for advanced hepatocellular carcinoma (HCC) not suitable for surgical or loco-regional therapies in patients with preserved liver function. Many second-line drugs are currently under investigation, but none has proven effective so far. Metronomic chemotherapy is characterized by antiangiogenic activity as well and good tolerability. Therefore we started a phase II clinical study to assess efficacy of metronomic capecitabine in advanced HCC patients. Methods: This phase II trial allowed inclusion of 90 HCC patients (pts) in two sub-studies: first-line systemic treatment (60 pts) and second-line after sorafenib (30 pts.) Main inclusion criteria were Child-Pugh liver function class A and progressive disease not candidate for surgery or loco-regional treatments. Treatment schedule was capecitabine 500 mg bid after meals continuously. In case of severe toxicity up to two weeks off-therapy were permitted for recovery; no dose adjustment was allowed. Primary endpoint is three-months progression-free survival rate (PFS3mo), assessed by RECIST 1.1. This preliminary analysis aims at evaluating efficacy and toxicity of metronomic capecitabine after progression on sorafenib treatment. Results: Patients\u2019 accrual ended in December 2010. A total of 30 pts pre-treated with sorafenib have been included; of these, 12 had relapsed after surgery and 24 had been previously managed with percutaneous ablations or chemoembolizations. 23 pts are currently assessable for efficacy. We observed no objective responses, 9 stable disease and 14 progressive disease, for a PFS3mo of 39%. Overall and progression-free survival will be evaluated in a further analysis with longer follow-up. All patients are assessable for toxicity. The most common adverse events were asthenia, nausea, diarrhoea and pruritus, generally mild and tolerable. Conclusions: Metronomic capecitabine is well tolerated and can be active in HCC patients after progression under sorafenib treatment. The extent of clinical benefit will be determined in the final analysis