Dataset Information

Phase 2 study of circulating microRNA biomarkers in castration-resistant prostate cancer.

ABSTRACT:

Background

Biomarkers of therapeutic response and prognosis are needed to assist in the sequencing of treatments for metastatic castration-resistant prostate cancer (CRPC). Previously in a Phase 1 discovery study, we identified 14 circulating microRNAs that were associated with response to docetaxel chemotherapy or overall survival. We performed a Phase 2 validation study to verify these findings.

Methods

Using real-time PCR, the levels of the 14 microRNAs were measured in plasma collected before and after the first cycle of docetaxel from a Phase 2 cohort of 89 patients.

Results

The microRNAs were not associated with docetaxel response in the Phase 2 cohort. Higher baseline levels of six microRNAs, predominantly of the miR-200 family, were confirmed to be associated with shorter overall survival. A microRNA signature comprising these six microRNAs predicted high-risk patients in the Phase 2 cohort with a hazard ratio of 4.12 (95% CI 2.20-7.70, P=0.000001). The signature was an independent predictor in multivariable analysis with clinicopathological factors.

Conclusions

The association of circulating microRNAs with overall survival suggests their involvement in CRPC progression.

SUBMITTER: Lin HM

PROVIDER: S-EPMC5396108 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Publications

Phase 2 study of circulating microRNA biomarkers in castration-resistant prostate cancer.

Lin Hui-Ming HM Mahon Kate L KL Spielman Calan C Gurney Howard H Mallesara Girish G Stockler Martin R MR Bastick Patricia P Briscoe Karen K Marx Gavin G Swarbrick Alexander A Horvath Lisa G LG

British journal of cancer 20170309 8

<h4>Background</h4>Biomarkers of therapeutic response and prognosis are needed to assist in the sequencing of treatments for metastatic castration-resistant prostate cancer (CRPC). Previously in a Phase 1 discovery study, we identified 14 circulating microRNAs that were associated with response to docetaxel chemotherapy or overall survival. We performed a Phase 2 validation study to verify these findings.<h4>Methods</h4>Using real-time PCR, the levels of the 14 microRNAs were measured in plasma ...[more]

PMID: 28278515

Similar Datasets

Project description:BackgroundEndothelial progenitor cells (CEPs) and circulating endothelial cells (CECs) are potential biomarkers of response to anti-angiogenic treatment regimens. In the current study, we investigated the effect of docetaxel and sunitinib on CEP/CEC kinetics and clinical response in castration resistant prostate cancer (CRPC) patients.Patients and methodsChemonaive patients with CRPC were enrolled in this study to receive either sunitinib (37.5 mg/d), in combination with docetaxel (75 mg/m2) or docetaxel alone. CEP and CEC kinetics were analyzed for every cycle. The primary objective was to compare CEP/CEC pharmacodynamics between both treatment arms. We also investigated if CEC/CEP spikes, induced by MTD docetaxel, are suppressed by sunitinib in patients treated with docetaxel/sunitinib relative to docetaxel monotherapy.ResultsA total of 27 patients were enrolled. We observed a significant increase of CEP/CEC (total/viable) counts over time within each cycle (coefficients 0.29233, 0.22092 and 0.26089, respectively; p<0.001). However, no differences between the treatment groups, in terms of CEP and CEC kinetics, were detected. In the docetaxel monotherapy arm 4 (30%) patients responded to therapy with a 50% PSA decline, while 9 (64%) patients showed a PSA decline in the combination group (n.s.). The median PFS in the docetaxel monotherapy group was 3.1 months (2.6-3.6 months, 95% CI) and 6.2 months (4.9-7.4 months, 95% CI; p = 0.062) in the combination arm. Sunitinib/docetaxel was reasonably well tolerated and toxicity manageable.ConclusionIn summary, no significant differences in CEC and CEP kinetics between the treatment arms were observed, although a highly significant increase of CEPs/CECs within each cycle over time was detected. These results mirror the challenge we have to face when employing anti-angiogenic strategies in CRPC. Additional preclinical research is needed to elucidate the underlying molecular mechanisms. However, docetaxel/sunitinib therapy resulted in a better response in terms of PSA decline and a trend towards improved PFS.Trial registeryclinicaltrialsregister.eu EudraCT 2007-003705-27.

Dataset Information

Phase 2 study of circulating microRNA biomarkers in castration-resistant prostate cancer.

Background

Methods

Results

Conclusions

Publications

Phase 2 study of circulating microRNA biomarkers in castration-resistant prostate cancer.

Similar Datasets

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