2016 ASCO: Epigenetic resensitization in recurrent, platinum-resistant OC using SGI-110: Phase 2 results

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 hypomethylatingagent, in combination with carboplatin demonstrated activity in recurrent platinum resistant ovarian cancer patients (Matei et al. Cancer Research 2012)
Guadecitabine is a dinucleotide of decitabine and deoxyguanosine, affords increased in vivo exposure of decitabine by protecting it from deamination due to slow release upon SQinjection
In Phase 1 studies, guadecitabine provides longer exposure and more potent hypomethylationcompared to decitabine. Combining guadecitabine with carboplatin in this population may improve upon the encouraging preliminary results and an acceptable dose for phase 2 was previously established (Fleming, et al AACR 2014)

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