Discussion and conclusion Until recently, no systemic treatment has shown any ben efits for patients with advanced HCC. The breakthrough results obtained with sorafenib have represented a major step in the management of this deadly disease that now has an option of similar efficacy as that of agents used for other cancers such cell assay as lung and colorectal. Unfortu nately the impact of sorafenib is not the final answer. Tumor growth is significantly delayed and survival is improved, but ultimately the HCC progresses and patients die because of cancer. Inhibitors,Modulators,Libraries This shows the need to develop new agents that would further expand the bene fits of current therapy. Major interest is being placed in the evaluation of other molecular therapies to be given in association to sorafenib or upon sorafenib failure, thus opening the field for second line options.

In addition to agents modulating the Inhibitors,Modulators,Libraries activation of signaling cascades, there is a known potential in priming immune response against cancer cells to overcome the immune escape that malignant cells are able to establish as a prominent fea ture. Several approaches to induce immune reactiva tion to control cancer have been tested. In this investigation, we have evaluated the effect of a telomerase derived peptide vaccine in combination with low dose cyclophosphamide treatment in a single arm phase II trial. The primary efficacy variable for this study was overall response. however, there were no complete or partial responses during this study. The best overall tumor response for the ITT popu lation was stable Inhibitors,Modulators,Libraries disease for 17 patients.

In a recent placebo controlled phase III study on Sorafenib in advanced HCC patients, none of the patients had a complete response, but 2% of the patients in the Sorafenib group had a partial response and 71% had stable disease maintained for at least 28 days after the first demonstration. However, in the Sorafenib Inhibitors,Modulators,Libraries study, tumor measurements were per formed every 6 weeks Inhibitors,Modulators,Libraries whereas in the present study CT scans were performed every 8 weeks, which makes direct comparison of tumor response between studies difficult. Nonetheless, the TTP detected in our study with a less frequent timing is shorter than that registered both in the SHARP and in the Asian Pacific trials. Hence, vaccine therapy using GV1001 has not evidenced any efficacy in terms of tumor response and TTP.

This has been recently suggested to be the optimal end point to register the potential efficacy EPZ-5676 mll of agents where no major reduction in tumor mass is to be expected. The validity of the con cept has been shown in the sorafenib studies and cur rently, most investigations are designed to capture at the same time TTP and tumor response according to conven tional RECIST with the modifications reflected in the JNCI AASLD guidelines.