2014 AACR: Clinical epigenetic resensitization of platinum-resistant recurrent ovarian cancer

Summary

In the past 20 years there has been little change in the 1‐, 3‐, and 5‐ year survival rates for patients with ovarian cancer
5‐year survival is ~25% for patients diagnosed with advanced stage disease
Recurrence is common and patients develop resistance to chemotherapy
Platinum resistant ovarian cancer is uniformly fatal and epigenetic changes have been implicated in the development of platinum resistance
Previous experience with decitabine, a hypomethylating agent, in combination with carboplatin demonstrated activity in recurrent platinum resistant ovarian cancer patients (Matei et al. Cancer Research 2012)
SGI‐110 is a dinucleotide of decitabine and deoxyguanosine, affords increased in vivo exposure of decitabine by protecting it from deamination due to slow release upon SQ injection
In Phase 1 studies, SGI‐110 provides longer exposure and more potent hypomethylation compared to decitabine. Combining SGI‐110 with carboplatin in this population may improve upon the encouraging preliminary results