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Carboplatin with Decitabine Therapy, in Recurrent Platinum Resistant Ovarian Cancer, Alters Circulating miRNAs Concentrations: A Pilot Study.
- Source :
-
PloS one [PLoS One] 2015 Oct 20; Vol. 10 (10), pp. e0141279. Date of Electronic Publication: 2015 Oct 20 (Print Publication: 2015). - Publication Year :
- 2015
-
Abstract
- Objective: Plasma miRNAs represent potential minimally invasive biomarkers to monitor and predict outcomes from chemotherapy. The primary goal of the current study-consisting of patients with recurrent, platinum-resistant ovarian cancer-was to identify the changes in circulating miRNA concentrations associated with decitabine followed by carboplatin chemotherapy treatment. A secondary goal was to associate clinical response with changes in circulating miRNA concentration.<br />Methods: We measured miRNA concentrations in plasma samples from 14 patients with platinum-resistant, recurrent ovarian cancer enrolled in a phase II clinical trial that were treated with a low dose of the hypomethylating agent (HMA) decitabine for 5 days followed by carboplatin on day 8. The primary endpoint was to determine chemotherapy-associated changes in plasma miRNA concentrations. The secondary endpoint was to correlate miRNA changes with clinical response as measured by progression free survival (PFS).<br />Results: Seventy-eight miRNA plasma concentrations were measured at baseline (before treatment) and at the end of the first cycle of treatment (day 29). Of these, 10 miRNAs (miR-193a-5p, miR-375, miR-339-3p, miR-340-5p, miR-532-3p, miR-133a-3p, miR-25-3p, miR-10a-5p, miR-616-5p, and miR-148b-5p) displayed fold changes in concentration ranging from -2.9 to 4 (p<0.05), in recurrent platinum resistant ovarian cancer patients, that were associated with response to decitabine followed by carboplatin chemotherapy. Furthermore, lower concentrations of miR-148b-5p after this chemotherapy regimen were associated (P<0.05) with the PFS.<br />Conclusions: This is the first report demonstrating altered circulating miRNA concentrations following a combination platinum plus HMA chemotherapy regiment. In addition, circulating miR-148b-5p concentrations were associated with PFS and may represent a novel biomarker of therapeutic response, with this chemotherapy regimen, in women with recurrent, drug-resistant ovarian cancer.
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Azacitidine administration & dosage
Azacitidine analogs & derivatives
Biomarkers, Tumor blood
Carboplatin administration & dosage
Decitabine
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Humans
MicroRNAs blood
Middle Aged
Neoplasm Recurrence, Local genetics
Neoplasm Recurrence, Local mortality
Neoplasm Recurrence, Local pathology
Neoplasm Staging
Ovarian Neoplasms genetics
Ovarian Neoplasms mortality
Ovarian Neoplasms pathology
Pilot Projects
Prognosis
Survival Rate
Young Adult
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Biomarkers, Tumor genetics
Drug Resistance, Neoplasm genetics
MicroRNAs genetics
Neoplasm Recurrence, Local drug therapy
Ovarian Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 10
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 26485143
- Full Text :
- https://doi.org/10.1371/journal.pone.0141279