Dataset Information

Efficacy of tasquinimod in men with metastatic castration-resistant prostate cancer: A meta-analysis of randomized controlled trials.

ABSTRACT:

Background

Tasquinimod is an oral quinoline-3-carboxamide derivative for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Tasquinimod has antiangiogenic, immunomodulatory, and antimetastatic properties, but it is also associated with toxicities, including skeletal pain, digestive disorders, fatigue, insomnia, and mental disorders. We aimed to perform a meta-analysis to evaluate the efficacy, safety, and long-term survival for tasquinimod in patients with mCRPC.

Methods

Searches were carried out in PubMed, Embase, and the Cochrane Library. Eligible articles included randomized clinical trials (RCTs) comparing systemic or combination therapy (excluding primary or secondary androgen deprivation therapy, bone protective agents, or radionuclides) with placebo in men with mCRPC.

Results

Three RCTs were selected for final evaluation. The pooled results from the 3 studies indicated that tasquinimod was associated with good radiologic progression-free survival (rPFS) in mCRPC. For adverse effects (AEs), the results of meta-analysis indicated that patients with mCRPC who received tasquinimod had obvious anemia (risk ratio (RR) 1.35, 95% confidence interval (CI) 1.06-1.73, P?=?.02), back pain (RR: 1.57, 95% CI: 1.01-2.47, P?=?.05), pain in the extremities (RR: 1.90, 95% CI: 1.14-3.17, P?=?.01), insomnia (RR: 1.50, 95% CI: 1.03-2.17, P?=?.03), vomiting (RR: 1.52, 95% CI: 1.04-2.21, P?=?.03), and peripheral edema (RR: 1.52, 95% CI: 1.03-2.23, P?=?.03).

Conclusions

Tasquinimod is associated with better rPFS in mCRPC. The toxicity of tasquinimod requires further investigation, it is not recommended for routine clinical use.

SUBMITTER: Gong P

PROVIDER: S-EPMC6257339 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Efficacy of tasquinimod in men with metastatic castration-resistant prostate cancer: A meta-analysis of randomized controlled trials.

Gong Ping P Liu Hongjian H Liu Xinyu X Zhou Ge G Liu Meitian M Yang Xiaodi X Xiong Wenjing W Wang Qi Q Ma Juan J Ren Zheng Z He Minfu M Zhang Xiumin X

Medicine 20181101 46

<h4>Background</h4>Tasquinimod is an oral quinoline-3-carboxamide derivative for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Tasquinimod has antiangiogenic, immunomodulatory, and antimetastatic properties, but it is also associated with toxicities, including skeletal pain, digestive disorders, fatigue, insomnia, and mental disorders. We aimed to perform a meta-analysis to evaluate the efficacy, safety, and long-term survival for tasquinimod in patients with mCRPC.<h ...[more]

PMID: 30431595

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Project description:We have recently witnessed a rapid increase in the number of effective systemic agents for men with metastatic castration-resistant prostate cancer (CRPC), including novel hormonal therapies (abiraterone acetate and MDV3100), immunotherapies (sipuleucel-T), chemotherapies (cabazitaxel), and bone microenvironment targeting agents (denosumab, radium 223). Given the increasing complexity of treatment decisions for this disease, major research and clinical priorities are (1) finding biomarkers that enable an understanding of the natural history and complex biology of this heterogeneous malignancy, (2) defining predictive biomarkers that identify men most likely to benefit from a given therapy, and (3) identifying biomarkers of early response or progression to optimize outcomes.In this review, we discuss existing and potential biomarkers in CRPC and how they may currently inform prognosis, aid in treatment selection (predictive value), and relate to survival outcomes (surrogacy).PubMed-based literature searches and abstracts through September 2011 provided the basis for this literature review as well as expert opinion.We address blood and urine-based biomarkers such as prostate-specific antigen, lactate dehydrogenase, total and bone alkaline phosphatase and other bone turnover markers, hemoglobin, and circulating tumor cells in the context of prognosis, prediction, and patient selection for therapy. Given the inherent problems associated with defining progression-free survival in CRPC, the importance of biomarker development and the needed steps are highlighted. We place the discussion of biomarkers within the context of the design/intent of a trial and mechanism of action of a given systemic therapy. We discuss novel biomarker development and the pathway for surrogate or predictive biomarkers to become credentialed as useful tests that inform therapeutic decisions.A greater understanding of biomarkers in CRPC permits a more personalized approach to care that maximizes benefit and minimizes harm and can inform clinical trials tailored to men most likely to derive benefit.

Project description:BackgroundRadium-223 is a targeted alpha-particle therapy that improves survival in men with metastatic castration resistant prostate cancer (mCRPC), particularly in men with elevated serum levels of bone alkaline phosphatase (B-ALP). We hypothesized that osteomimicry, a form of epithelial plasticity leading to an osteoblastic phenotype, may contribute to intralesional deposition of radium-223 and subsequent irradiation of the tumor microenvironment.MethodsWe conducted a pharmacodynamic study (NCT02204943) of radium-223 in men with bone mCRPC. Prior to and three and six months after radium-223 treatment initiation, we collected CTCs and metastatic biopsies for phenotypic characterization and CTC genomic analysis. The primary objective was to describe the impact of radium-223 on the prevalence of CTC B-ALP over time. We measured radium-223 decay products in tumor and surrounding normal bone during treatment. We validated genomic findings in a separate independent study of men with bone metastatic mCRPC (n = 45) and publicly accessible data of metastatic CRPC tissues.ResultsWe enrolled 20 men with symptomatic bone predominant mCRPC and treated with radium-223. We observed greater radium-223 radioactivity levels in metastatic bone tumor containing biopsies compared with adjacent normal bone. We found evidence of persistent Cellsearch CTCs and B-ALP (+) CTCs in the majority of men over time during radium-223 therapy despite serum B-ALP normalization. We identified genomic gains in osteoblast mimicry genes including gains of ALPL, osteopontin, SPARC, OB-cadherin and loss of RUNX2, and validated genomic alterations or increased expression at the DNA and RNA level in an independent cohort of 45 men with bone-metastatic CRPC and in 150 metastatic biopsies from men with mCRPC.ConclusionsOsteomimicry may contribute in part to the uptake of radium-223 within bone metastases and may thereby enhance the therapeutic benefit of this bone targeting radiotherapy.

Dataset Information

Efficacy of tasquinimod in men with metastatic castration-resistant prostate cancer: A meta-analysis of randomized controlled trials.

Background

Methods

Results

Conclusions

Publications

Efficacy of tasquinimod in men with metastatic castration-resistant prostate cancer: A meta-analysis of randomized controlled trials.

Similar Datasets

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