Again and again I have mentioned the huge need we have for the development of reliable bio-markers. Reliable bio-markers will allow us to know which men will respond positively to a treatment (also those who will not) and when a treatment is still effective (also when it no longer is effective).
These biomarkers really don’t exist, so a lot of clinical decision-making is based upon the experience and gut feeling of our doctors. This type of decision-making is not adequate in today’s world of multiple treatment options, especially when many of the treatments can foster resistance to other available treatments.
To help define possible bio-markers for a positive clinical response and overall survival (OS) to Abiraterone (Zytiga), researchers evaluated alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and prostate specific antigen (PSA) in men with bone metastatic castrate resistant prostate cancer (bmCRPC).
They evaluated 84 men with 39 being at the pre-chemotherapy and 45 post-chemotherapy stages. They had a median follow up of 14.0 months.
The researchers observed a lot of very early, in treatment, ALP-Bouncing with Abiraterone therapy. ALP-Bouncing or rapidly rising ALP-levels independent of baseline ALP during the first 2–4 weeks of Abiraterone therapy coupled with subsequent equally marked decline to pre-treatment levels or better within 8 weeks of therapy, preceding potentially delayed PSA decline.
They found that the failure of a man having a PSA reduction greater than 50% and the failure of ALP-Bouncing were the strongest predictors of progressive prostate cancer.
They concluded that the rising ALP at 12 weeks, a PSA reduction less than 50% and no ALP-Bouncing were strongest predictors of poor overall survival.
They also found that there was worse OS in men with rising ALP at 12 weeks, a PSA reduction that was less than 50% and no ALP-Bouncing.
In subgroup-analysis of oligosymptomatic men, all parameters remained significant predictors of poor OS, with no PSA reduction greater than 50 % and rising ALP at 12 weeks being the strongest negative predictor.
PSA reduction that was greater than 50% remained an independent predictor of OS for all the men including the oligosymptomatic subgroup.
They also found that no man with a rising ALP at 12 weeks received any further benefit of Abiraterone. In this circumstance continuing Abiraterone was pointless.
Dynamic changes of ALP, LDH and PSA during Abiraterone therapy are associated with best clinical benefit and overall survival in bone positive mCRPC.
They also found that ALP-Bouncing occurring earlier than PSA-changes as well as prior to equivocal imaging results and rising ALP at 12 weeks under Abiraterone may help to decide whether to discontinue Abiraterone.
doi:10.1186/s12885-016-2260-y; Mikah, Krabbe, Eminaga, etal.
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