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Carboplatin with Decitabine Therapy, in Recurrent Platinum Resistant Ovarian Cancer, Alters Circulating miRNAs Concentrations: A Pilot Study.

Benson EA, Skaar TC, Liu Y, Nephew KP, Matei D - PLoS ONE (2015)

Bottom Line: Seventy-eight miRNA plasma concentrations were measured at baseline (before treatment) and at the end of the first cycle of treatment (day 29).Furthermore, lower concentrations of miR-148b-5p after this chemotherapy regimen were associated (P<0.05) with the PFS.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; VA Roudebush Hospital, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.

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.

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).

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.

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.

No MeSH data available.


Related in: MedlinePlus

Study Design: Platinum resistant ovarian cancer subjects treated with decitabine and carboplatin.Fourteen platinum resistant ovarian cancer patients were treated with decitabine/carboplatin in a phase II clinical trial. For the first chemotherapy cycle, decitabine was given daily for 5 days; followed by carboplatin given on day 8. miRNA analysis used plasma samples collected at baseline (prior to start of cycle one treatment) and at day 29 (prior to start of second cycle).
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pone.0141279.g001: Study Design: Platinum resistant ovarian cancer subjects treated with decitabine and carboplatin.Fourteen platinum resistant ovarian cancer patients were treated with decitabine/carboplatin in a phase II clinical trial. For the first chemotherapy cycle, decitabine was given daily for 5 days; followed by carboplatin given on day 8. miRNA analysis used plasma samples collected at baseline (prior to start of cycle one treatment) and at day 29 (prior to start of second cycle).

Mentions: Briefly, whole blood was collected in EDTA containing tubes, and then centrifuged to plasma. Samples used for microRNA analysis were collected at two time points: at baseline (prior to the start of the first cycle of treatment); and on day 29 after treatment initiation (post the first cycle of chemotherapy; Fig 1). Samples from 14 of the 17 patients were available for this miRNA analysis. The remaining 3 samples were not analyzed because of insufficient plasma. Samples were analyzed after the first cycle to allow for early miRNA analysis, which may provide evidence toward their future use in early clinical decision-making.


Carboplatin with Decitabine Therapy, in Recurrent Platinum Resistant Ovarian Cancer, Alters Circulating miRNAs Concentrations: A Pilot Study.

Benson EA, Skaar TC, Liu Y, Nephew KP, Matei D - PLoS ONE (2015)

Study Design: Platinum resistant ovarian cancer subjects treated with decitabine and carboplatin.Fourteen platinum resistant ovarian cancer patients were treated with decitabine/carboplatin in a phase II clinical trial. For the first chemotherapy cycle, decitabine was given daily for 5 days; followed by carboplatin given on day 8. miRNA analysis used plasma samples collected at baseline (prior to start of cycle one treatment) and at day 29 (prior to start of second cycle).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4612782&req=5

pone.0141279.g001: Study Design: Platinum resistant ovarian cancer subjects treated with decitabine and carboplatin.Fourteen platinum resistant ovarian cancer patients were treated with decitabine/carboplatin in a phase II clinical trial. For the first chemotherapy cycle, decitabine was given daily for 5 days; followed by carboplatin given on day 8. miRNA analysis used plasma samples collected at baseline (prior to start of cycle one treatment) and at day 29 (prior to start of second cycle).
Mentions: Briefly, whole blood was collected in EDTA containing tubes, and then centrifuged to plasma. Samples used for microRNA analysis were collected at two time points: at baseline (prior to the start of the first cycle of treatment); and on day 29 after treatment initiation (post the first cycle of chemotherapy; Fig 1). Samples from 14 of the 17 patients were available for this miRNA analysis. The remaining 3 samples were not analyzed because of insufficient plasma. Samples were analyzed after the first cycle to allow for early miRNA analysis, which may provide evidence toward their future use in early clinical decision-making.

Bottom Line: Seventy-eight miRNA plasma concentrations were measured at baseline (before treatment) and at the end of the first cycle of treatment (day 29).Furthermore, lower concentrations of miR-148b-5p after this chemotherapy regimen were associated (P<0.05) with the PFS.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; VA Roudebush Hospital, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.

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.

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).

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.

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.

No MeSH data available.


Related in: MedlinePlus