pl-88, page-6

Have read the P2 trial results you have quoted there. Are some concerns remaining that will likely be addressed in the P3 trial due out soon. From my point of view, it seems very unusual that the 160mg dose showed a trend to increasing time to recurrence whereas the 250mg dose did not (and was in fact similar to placebo). This is hard to explain as the higher dose should be more efficacious, albeit with more side effects. Just something to consider....

Here is a paragraph discussing the trial limitations:

"There are, however, several important limitations to consider regarding our present data. First, the case number was not sufficiently large to draw firm conclusions regarding the benefits of PI-88. Second, the enrolled patients were not stratified according to prognostic factors (CLIP score, HBV infection status, microvascular invasions, tumor status, liver function, ECOG performance status, etc). Moreover, although we found that the time to recurrence was greater in the patients treated with PI-88 160 mg/day compared with the controls, the influence of patient heterogeneity cannot be neglected at this stage. Third, we did not stratify our findings according to levels of the therapeutic target, heparanase, in either the HCC tissue or body fluids. Fourth, the follow-up period after PI-88 treatments was not long enough to demonstrate an overall survival advantage, considered by many to be the gold standard endpoint of cancer drug trials [2], [31] and [32]. At the same time, we preliminarily only assessed the non-recurrence rate of HCC at the end of the first stage of the study. In future clinical trials, time to recurrence should be adopted as the primary efficacy endpoint. Fifth, many new molecular target inhibitors for the treatment of advanced HCC have been identified recently. For example, sorafenib, an inhibitor of angiogenesis and Raf kinase, has recently shown to have efficacy in an unresectable setting [33]. The role of these new target inhibitors as adjuvant therapies after curative resection for HCC awaits further studies. Finally, we adopted the clinically commonly used radiographic or histologic criteria to define the presence of tumor recurrence and then the time to tumor recurrence in the present trial. Notably, the definition of time to recurrence was recently recommended in the RECIST amendments as the time from randomization to the time when recurrence was first suspected by regular CT or MRI study [30]. To address this issue, we re-analyzed our data based on the new definition. And we obtained similar results (data now shown). In the future, this definition should be followed to facilitate comparability of results obtained from other HCC trials."