61,64,65
Based on limited randomized studies, whereas CAD appears appropriate for BAY 11-7082 molecular weight patients with advanced metastatic prostate cancer, according to a study by Shore and Crawford IAD may be appropriate for many patients who reach castrate T levels (< 20 ng/dL) and a PSA nadir of < 4.0 ng/dL during induction therapy.63 However, the clinical benefits of maintaining T levels < 20 ng/dL versus < 50 ng/dL have not been prospectively studied. Carefully designed, prospective, randomized, phase III trials are needed Inhibitors,research,lifescience,medical for further assessment, with results clarifying issues such as selection of the most appropriate patients to receive IAD, optimal thresholds for stopping/resuming therapy, suitable ADT agents, and confirmation of the efficacy of IAD to mitigate serious adverse events. Does T Level Influence Survival Following ADT? Controversy previously existed regarding the clinical significance Inhibitors,research,lifescience,medical of circulating androgens following treatment with GnRH agonists. There is evidence that very low levels of T and its metabolites may elicit prostate cancer progression. Although the treatment is controversial, Inhibitors,research,lifescience,medical some experts believe that MAB (medical or surgical castration in combination with an antiandrogen) achieves superior survival over GnRH agonists alone.66 It is unclear whether this modest observed survival advantage
is attributable to prevention of the T flare or T escape, or suppression of adrenal androgens. There is new evidence that prostate cancers themselves are capable of synthesizing endogenous T.67 A recent Inhibitors,research,lifescience,medical clinical study showing that treatment with a CYP17 inhibitor such as abiraterone, either alone or with glucocorticoids, resulted in significant
antitumor activity Inhibitors,research,lifescience,medical in patients with androgen independent progression (AIP) both who had and had not received chemotherapy.68 The goal of pharmacologic castration is to achieve T suppression comparable with surgical castration. Historically, it was assumed that surgical castration achieved T levels < 1.5 pmol/L because this was the lower limit for assaying T also levels at the time.69 Therefore, GnRH agonists were assumed to achieve equivalence to surgical castration if they achieved T levels < 50 ng/dL. Using newer chemiluminescent techniques,70 it was subsequently shown in a single study that surgical castration achieves median T levels equivalent to 15 ng/dL.9 Ideally, this should be the goal of GnRH agonists. There are two recent studies suggesting that consistent T suppression < 50 ng/dL following GnRH agonists can be associated with superior survival. Morote and colleagues21 and Perachino and colleagues10 hypothesized that progression and survival following administration of GnRH agonists is related to the degree of T suppression.
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