PSADT as a surrogate for drug activity

PSA is one of the major androgen receptor-dependent target genes [27], and clinical monitoring is used to detect early stage disease as well as the emergence of recurrent tumor after therapy [28, 29, 30] and changes mirror changes in tumor bulk and indicate response to drugs. The graphic representation of PSA-DT is illustrated and its formula is given in Figure 4 [26].

Kelloff et al. [31], reviewed the use of PSA-DT as a surrogate for tumor response to drugs in patients with prostate cancer. They concluded that protocols that demonstrate significant changes in PSA-DT might be used to support accelerated approval of newer therapies. There is data to suggest PSA-DT in castrate resistant patients is predictive of outcome after chemotherapy [32]. An important caveat is expressed by Newling's review [33] of the subject which concluded that though dynamic changes in the PSA such as PSA-DT are commonly used in clinical trials of new drug therapies, PSA-DT might be affected by other factors including assay variations and false elevations of serum PSA caused by irritation of bladder catheters, prostatitis and cystitis. A substantial incidence of transient elevations of PSA (55%) was reported following combined external beam radiation and brachytherapy for prostate cancer [34]. These complicating issues should always be considered before PSA-DT is used to modify therapy.

Most recently, newer targeted and immunotherapies were found to produce paradoxical effects on PSA kinetics. Newling [33] argues that PSA should therefore be used as a secondary end point while overall survival still remains the gold standard in evaluating therapeutic efficacy for patients with hormone refractory disease.

0 0

Post a comment