STOCKHOLM—Elesclomol, an investigational small-molecule oxidative stress inducer (Synta Pharmaceuticals), in combination with paclitaxel (Taxol) showed a trend toward improved survival in stage IV metastatic melanoma patients, compared with paclitaxel alone. Steven O’Day, MD, of The Angeles Clinic and Research Institute in Los Angeles, reported the findings from a stage II study at ESMO 2008.
Elesclomol rapidly induces reactive oxygen species (ROS) in melanoma cells, causing them to activate signaling pathways that lead to apoptosis. The compound is known to synergize with taxanes, which by themselves are not very effective in melanoma. “Elesclomol accentuates apoptosis by synergizing with Taxol chemotherapy,” Dr. O’Day explained.
The multicenter study randomized 81 stage IV metastatic patients with one or no prior therapies to paclitaxel 80 mg/m2 alone or paclitaxel co-infused with elesclomol 213 mg/m2. Treatment was administered once weekly for 3 weeks, followed by 1 week off, until disease progression. Nineteen paclitaxel-treated patients crossed-over to the combination upon progression. At 21 months of follow-up, median-overall survival was 11.9 months with the combination vs 7.8 months with paclitaxel alone, representing a 22% reduction in risk of death (not statistically significant).
Overall survival, which Dr. O’Day noted was confounded by crossover, was 49% and 43%, respectively, at 1 year, and 27% and 21%, respectively, at 2 years. Response rates were 15.1% with the combination and 3.6% with paclitaxel alone. Dr. O’Day said that over half the subjects receiving the experimental regimen achieved disease control (CR, PR, SD) and 35% of patients treated with the combination were without progression at 6 months compared with 15% in the Taxol control arm alone.
ESMO session chair Ulrich Keilholz, MD, of Charite University in Berlin commented that the study results strongly support the ongoing international phase III SYMMETRY trial, which will enroll 630 patients in 150 centers in 15 countries, including Australia, Germany, Romania, Spain, and the U.S.
In November 2006, elesclomol received a fast track development designation from the US Food and Drug Administration.