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Mechanism of action and clinical activity of tasquinimod in castrate-resistant prostate cancer.

Gupta N, Al Ustwani O, Shen L, Pili R - Onco Targets Ther (2014)

Bottom Line: Over the past 3 years, significant advances in the field have been made with US Food and Drug Administration approval of new drugs for patients with CRPC.Tasquinimod is a second-generation quinoline-3-carboxamide agent that is currently in final stages of clinical development as a treatment for CRPC.The preclinical studies of tasquinimod have formed the basis for its success as an antiangiogenic and immunomodulatory agent in this disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.

ABSTRACT
Castrate-resistant prostate cancer (CRPC) is a disease where survival is poor and treatment is challenging. Over the past 3 years, significant advances in the field have been made with US Food and Drug Administration approval of new drugs for patients with CRPC. However, despite the presence of new approved drugs such as enzalutamide, abiraterone, sipuleucel-T, cabazitaxel, and alpharadin, there is still an unmet need for novel agents with different mechanisms of action to target CRPC. Based on earlier studies demonstrating therapeutic potential of a quinoline-3-carboxamide agent roquinimex as an anticancer drug, efforts were directed to identify other useful members in this class. Tasquinimod is a second-generation quinoline-3-carboxamide agent that is currently in final stages of clinical development as a treatment for CRPC. The preclinical studies of tasquinimod have formed the basis for its success as an antiangiogenic and immunomodulatory agent in this disease. Tasquinimod is an orally available agent that has shown efficacy and favorable safety profile as deduced by the results of Phase I and II clinical trials of this drug in prostate cancer. The place of tasquinimod in the treatment of CRPC patients is currently under examination in an ongoing Phase III clinical trial. In this review, we will discuss tasquinimod, starting from its discovery and current knowledge on potential mechanisms of action to its clinical potential in CRPC.

No MeSH data available.


Related in: MedlinePlus

Schema for current tasquinimod Phase III study.Abbreviation: CRPC, castrate-resistant prostate cancer.
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f4-ott-7-223: Schema for current tasquinimod Phase III study.Abbreviation: CRPC, castrate-resistant prostate cancer.

Mentions: Currently, there are three ongoing clinical trials on tasquinimod in prostate cancer (NCT01234311, NCT01732549,57,58 NCT0151373355) as described below. Table 4 shows the list of ongoing clinical trials related to tasquinimod in prostate cancer. A Phase III randomized, double-blind, placebo-controlled study of tasquinimod (NCT0123431157) is being conducted currently in asymptomatic to mildly symptomatic patients with metastatic CRPC to confirm the effect of tasquinimod on delaying disease progression compared with placebo. Approximately 1,200 eligible patients with metastatic CRPC are to be randomly assigned in a 2:1 ratio to either tasquinimod or placebo. Variable doses of tasquinimod ranging from 0.25 to 1.00 mg daily are being used in the trial. Eligible patients include males with histologically confirmed diagnosis of adenocarcinoma of prostate, with evidence of bone-metastatic disease on radiographic examination, castrate levels of serum testosterone <50 ng/dL, people with Karnofsky score of >70%, and no evidence of prior malignancies. Major exclusion criteria constitute prior cytotoxic chemotherapy for prostate cancer within 2 years, previous radiotherapy, biological therapy or antiandrogens within 4 weeks, and opiate or radiotherapy requirement for prostate cancer pain. Although the study is powered for OS analysis, the primary endpoint is PFS defined as the time from the date of randomization to the date of radiological progression or death. Figure 4 shows the schema of the inclusion criteria and clinical endpoints of the Phase III study.


Mechanism of action and clinical activity of tasquinimod in castrate-resistant prostate cancer.

Gupta N, Al Ustwani O, Shen L, Pili R - Onco Targets Ther (2014)

Schema for current tasquinimod Phase III study.Abbreviation: CRPC, castrate-resistant prostate cancer.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928061&req=5

f4-ott-7-223: Schema for current tasquinimod Phase III study.Abbreviation: CRPC, castrate-resistant prostate cancer.
Mentions: Currently, there are three ongoing clinical trials on tasquinimod in prostate cancer (NCT01234311, NCT01732549,57,58 NCT0151373355) as described below. Table 4 shows the list of ongoing clinical trials related to tasquinimod in prostate cancer. A Phase III randomized, double-blind, placebo-controlled study of tasquinimod (NCT0123431157) is being conducted currently in asymptomatic to mildly symptomatic patients with metastatic CRPC to confirm the effect of tasquinimod on delaying disease progression compared with placebo. Approximately 1,200 eligible patients with metastatic CRPC are to be randomly assigned in a 2:1 ratio to either tasquinimod or placebo. Variable doses of tasquinimod ranging from 0.25 to 1.00 mg daily are being used in the trial. Eligible patients include males with histologically confirmed diagnosis of adenocarcinoma of prostate, with evidence of bone-metastatic disease on radiographic examination, castrate levels of serum testosterone <50 ng/dL, people with Karnofsky score of >70%, and no evidence of prior malignancies. Major exclusion criteria constitute prior cytotoxic chemotherapy for prostate cancer within 2 years, previous radiotherapy, biological therapy or antiandrogens within 4 weeks, and opiate or radiotherapy requirement for prostate cancer pain. Although the study is powered for OS analysis, the primary endpoint is PFS defined as the time from the date of randomization to the date of radiological progression or death. Figure 4 shows the schema of the inclusion criteria and clinical endpoints of the Phase III study.

Bottom Line: Over the past 3 years, significant advances in the field have been made with US Food and Drug Administration approval of new drugs for patients with CRPC.Tasquinimod is a second-generation quinoline-3-carboxamide agent that is currently in final stages of clinical development as a treatment for CRPC.The preclinical studies of tasquinimod have formed the basis for its success as an antiangiogenic and immunomodulatory agent in this disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.

ABSTRACT
Castrate-resistant prostate cancer (CRPC) is a disease where survival is poor and treatment is challenging. Over the past 3 years, significant advances in the field have been made with US Food and Drug Administration approval of new drugs for patients with CRPC. However, despite the presence of new approved drugs such as enzalutamide, abiraterone, sipuleucel-T, cabazitaxel, and alpharadin, there is still an unmet need for novel agents with different mechanisms of action to target CRPC. Based on earlier studies demonstrating therapeutic potential of a quinoline-3-carboxamide agent roquinimex as an anticancer drug, efforts were directed to identify other useful members in this class. Tasquinimod is a second-generation quinoline-3-carboxamide agent that is currently in final stages of clinical development as a treatment for CRPC. The preclinical studies of tasquinimod have formed the basis for its success as an antiangiogenic and immunomodulatory agent in this disease. Tasquinimod is an orally available agent that has shown efficacy and favorable safety profile as deduced by the results of Phase I and II clinical trials of this drug in prostate cancer. The place of tasquinimod in the treatment of CRPC patients is currently under examination in an ongoing Phase III clinical trial. In this review, we will discuss tasquinimod, starting from its discovery and current knowledge on potential mechanisms of action to its clinical potential in CRPC.

No MeSH data available.


Related in: MedlinePlus