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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

Number of cycles of chemotherapy completed by each subject.The patients’ are numbered and ordered based on the number of received cycles of chemotherapy. Patients were separated by a red line to distinguish chemotherapy responders and non-responders. Responders remained free of disease progression for at least 6 cycles (n = 6); and non-responders remained free of disease progression less than 6 cycles (n = 8). Each cycle was 28 days long.
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pone.0141279.g002: Number of cycles of chemotherapy completed by each subject.The patients’ are numbered and ordered based on the number of received cycles of chemotherapy. Patients were separated by a red line to distinguish chemotherapy responders and non-responders. Responders remained free of disease progression for at least 6 cycles (n = 6); and non-responders remained free of disease progression less than 6 cycles (n = 8). Each cycle was 28 days long.

Mentions: Fourteen of the original 17 patients in the parent trial had plasma samples available for miRNA analysis. Disease status was assessed using RECIST and CA-125 criteria every 2 cycles of chemotherapy. Chemotherapy was discontinued with recording of an intolerable toxicity or disease progression. Disease progression in patients prior to 6 cycles (n = 8) of chemotherapy were considered non-responders; and disease progression after 6 cycles (n = 6) of chemotherapy were considered responders. Of the responders, one patient remained without progressive disease for ~17 months. Each patient completed the number of cycles of chemotherapy shown in Fig 2. The responders and non-responders are separated by the red line.


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)

Number of cycles of chemotherapy completed by each subject.The patients’ are numbered and ordered based on the number of received cycles of chemotherapy. Patients were separated by a red line to distinguish chemotherapy responders and non-responders. Responders remained free of disease progression for at least 6 cycles (n = 6); and non-responders remained free of disease progression less than 6 cycles (n = 8). Each cycle was 28 days long.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0141279.g002: Number of cycles of chemotherapy completed by each subject.The patients’ are numbered and ordered based on the number of received cycles of chemotherapy. Patients were separated by a red line to distinguish chemotherapy responders and non-responders. Responders remained free of disease progression for at least 6 cycles (n = 6); and non-responders remained free of disease progression less than 6 cycles (n = 8). Each cycle was 28 days long.
Mentions: Fourteen of the original 17 patients in the parent trial had plasma samples available for miRNA analysis. Disease status was assessed using RECIST and CA-125 criteria every 2 cycles of chemotherapy. Chemotherapy was discontinued with recording of an intolerable toxicity or disease progression. Disease progression in patients prior to 6 cycles (n = 8) of chemotherapy were considered non-responders; and disease progression after 6 cycles (n = 6) of chemotherapy were considered responders. Of the responders, one patient remained without progressive disease for ~17 months. Each patient completed the number of cycles of chemotherapy shown in Fig 2. The responders and non-responders are separated by the red line.

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