A phase I study of a hypomethylating agent azacitidine in combination with carboplatin in patients with platinum resistant epithelial ovarian cancer

5087 Background: Hypermethylation is a common event associated with inactivation of a variety of genes and pathways involved in tumorigenesis and progression as well as drug resistance. Previous evidence displayed that hypomethylating agents could resensitize epithelial ovarian cancer cells to platinum treatment through reexpression of platinum sensitivity-related genes. Therefore, it is of great interest to use a hypomethylating agent to resensitize platinum resistant epithelial ovarian cancer cells to platinum treatment. Methods: This proof-of-concept study used a modified dose-escalation schema (3+3 design). All patients, who have progressed within the 6 months after a platinum-based regimen, are eligible if they have a pathologically confirmed epithelial ovarian cancer. All patients receive subcutaneous injection of azacitidine 75 mg/m2/day for 5 days on days 1–5 and intravenous infusion of carboplatin once on day 2 of each treatment cycle (28 days). Azacitidine is maintained at the same dosage during dose-escalation of carboplatin from AUC4 to AUC5. Results: Six patients have received a total of 16 cycles of treatment. There was no grade 2 or higher toxicity observed. Three patients were evaluable for response: 1 patient, who received 6 cycles of treatment, achieved complete response by CA125 criteria and stable disease by imaging criteria; 1 patient, who received 5 cycles of treatment, displayed stable disease; and the 3rd patient, who received 2 cycles of treatment, showed mixed response by imaging criteria. Conclusions: Preliminary data showed that a regimen of azacitidine 75 mg/m2/day for 5 days plus carboplatin AUC 5 on day 2 was well tolerated in patients with extensive prior treatment. No significant financial relationships to disclose.