September 29, 2011 (Stockholm, Sweden) — The largest randomized phase 3 study ever conducted in patients with advanced malignant pleural mesothelioma has failed; no survival benefit was seen with vorinostat (Zolinza, Merck & Co).

Sadly yes, out of 660 patients, there was no significant difference in median overall survival between the vorinostat and placebo groups.

The latest article from Dr. Barbone and colleagues sheds some light on possible reasons for the unsuccessful outcome of the trial.

The chemoresistance of solid tumors such as mesothelioma may be better studied in vitro 3D models because multicellular spheroids acquire multicellular resistance that may recapitulate the stubborn chemoresistance seen in vivo.
Dr. Xiang et al. recently used multicellular spheroids to test the efficacy of the recombinant anti-mesothelin immunotoxin SS1P in spheroids. The authors compared 2D (monolayer) and 3D (multicellular spheroid) mesothelioma cultures of the cell line NCI-H226 and found that, regardless of equal mesothelin expression in 2D and in 3D, SS1P was at least 100 times less cytotoxic in spheroids compared …