Low Dose Decitabine Combined with Taxol and Platinum Chemotherapy to Treat Refractory/Recurrent Ovarian Cancer: An Open-Label, Single-Arm, Phase I/II Study.
OBJECTIVE
Previous research has proposed that the hypomethylating agent decitabine can sensitize ovarian cancer cells to chemical agents. In this open-label, phase I/II clinical study, we analyzed the toxicity and efficacy of low dose decitabine combined with taxol and platinum chemotherapy in treatment of refractory and recurrent ovarian cancer.


METHODS
Decitabine was administered intravenously at 7 mg/m(2) for 30 minutes over five consecutive days and followed by reduced dose taxol and platinum chemotherapy treatment (TC) every 28 days for at least four cycles. Adverse events (AEs) were graded according to the Common Terminology Criteria for AEs (NCI-CTCAE), and efficacy was assessed using the Response Evaluation Criteria in Solid Tumors assessment (RECIST).


RESULTS
Twenty-one patients diagnosed with relapsed/refractory ovarian cancer were initially enrolled in this study, and 17 patients were able to be evaluated. The combination of low dose decitabine and TC was well-tolerated. The most common adverse effects were nausea (77.8%) and neutropenia (66.7%), and adverse events greater than Grade 4 were not observed. The clinical benefit rate (CBR) was 70.6% (12/17), and the partial response (PR) and stable disease (SD) rates were 17.6% (3/17) and 52.9% (9/17), respectively. A significant decrease in serum CA125 levels was observed in many of the responsive cases even after completing the first treatment cycle.


CONCLUSIONS
Low dose decitabine combined with taxol and platinum was well-tolerated and suitable for treating refractory/refractory ovarian cancer. The change in CA125 levels might be a potential predictor for patient clinical response. The efficacy of low dose decitabine for treatment of ovarian cancer requires more volunteers for further investigation.
Xiaoyu
X
Fu
Yan
Y
Zhang
Xiaohui
X
Wang
Meixia
M
Chen
Yao
Y
Wang
Jing
J
Nie
Yuanguang
Y
Meng
Department of Bio-therapy, College of Life Sciences, Chinese PLA General Hospital, Beijing, 100853, China. hanwdrsw69@yahoo.com.
Weidong
W
Han
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D001374:Azacitidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D010984:Platinum / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D012008:Recurrence; D012449:Safety
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D010984:Platinum; D000077209:Decitabine; D001374:Azacitidine; D017239:Paclitaxel