Fosfataza zasadowa (ALP) w mCRPC (art. w j. ang.)

Fosfataza zasadowa (ALP) w mCRPC (art. w j. ang.)

Nieprzeczytany postautor: zosia bluszcz » 11 maja 2019, 02:28

Alkaline phosphatase in metastatic castration-resistant prostate cancer: reassessment of an older biomarker
Published Online: 21 Jun 2018

Since most patients with metastatic castration-resistant prostate cancer (mCRPC) have bone metastases, it is important to understand the potential impact of therapies on prognostic biomarkers, such as ALP. Clinical studies involving mCRPC life-prolonging agents (i.e., sipuleucel-T, abiraterone, enzalutamide, docetaxel, cabazitaxel, and radium-223) have shown that baseline ALP level is prognostic for overall survival, and may be a better prognostic marker for overall survival than prostate-specific antigen in patients with bone-dominant mCRPC. Mechanism of action differences between therapies may partly explain ALP dynamics during treatment. ALP changes can be interpreted within the context of other parameters while monitoring disease activity to better understand the underlying pathology. This review evaluates the current role of ALP in mCRPC.


Executive summary

Alkaline phosphatase in bone-metastatic castration-resistant prostate cancer


=> bALP is an enzyme that is expressed on the surface of osteoblasts; increased levels can indicate either a disease state or healing that is occurring within the bone.

=> In the absence of extensive liver disease, bALP is the primary component of serum total ALP (tALP) levels measured in patients with metastatic castration-resistant prostate cancer (mCRPC).

=> bALP level is used as a bone turnover marker reflective of a combination of osteoblastic activity and extent of disease (i.e., volume of metastases) in patients with bone-dominant mCRPC.


Clinical importance of ALP

=> ALP is a prognostic biomarker in mCRPC, reflecting disease outcome independent of therapy.

=> High baseline ALP levels are associated with negative outcomes, including skeletal complications and decreased survival, in patients with mCRPC.

=> Baseline ALP is a relevant prognostic marker for overall survival (OS) in bone-dominant mCRPC, along with others (e.g., prostate-specific antigen).

=> Changes in ALP levels may reflect changes in bone turnover and osteoblastic activity indicative of the extent of bone-metastatic disease.


Mechanism of action impact on ALP levels

=> Six drugs are currently approved for the treatment of mCRPC, based on their ability to prolong survival versus placebo or active comparator in Phase III clinical trials: sipuleucel-T, abiraterone acetate, enzalutamide, docetaxel, cabazitaxel and radium-223 dichloride.

=> Differences in mechanism of action between the life-prolonging therapies may partly explain ALP dynamics observed during treatment, especially within the initial period after starting a new therapeutic regimen.


ALP and life-prolonging mCRPC therapies

Clinical studies involving life-prolonging agents in mCRPC have shown that baseline ALP level is prognostic for OS independent of therapy selection; however, ALP level during treatment does not appear to be a confirmed predictive marker for OS.


Using ALP as a biomarker

=> tALP measurement, which is inexpensive and readily available, can provide valuable insight into changes occurring in the bone and may aid in the diagnosis of bone metastases.

=> Serial ALP measurements are useful, regardless of the therapy used to treat mCRPC.

=> Monitoring ALP levels in mCRPC can provide prognostic information about the likely outcome of the disease, but changes in ALP have not been validated as a surrogate for effectiveness of mCRPC therapy.

=> Reassuring patients about monitoring changes other than prostate-specific antigen is a crucial part of the clinician's communication with patients and caregivers.

=> It is not recommended that treatment be stopped solely based on changes in ALP; other indicators of disease progression are clearly needed.

https://www.futuremedicine.com/doi/full ... -2018-0087
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