[Efficacy and Prognostic Factors of Estracyt ® in Patients with Castration-Resistant Prostate Cancer (CRPC) : From the Data Analysis of Estracyt ® Special Drug Use Investigation].

Estracyt○R (estramustine phosphate) is a medical drug for prostate cancer with cytotoxic activity causing disruption of microtubule organization and indirect androgen production suppressing activity by its metabolite, estradiol. Based on the data obtained from the Estracyt○R Special Drug Use Investigation which surveyed the clinical efficacy and safety of Estracyt○R in patients with prostate cancer whose relapse of prostate cancer after combined androgen blockade (CAB) therapy was confirmed, we evaluated the progression-free survival, prognostic factor, decrease in prostate specific antigen (PSA) level and safety. This surveillance was conducted at 147 institutions nationwide between October, 2010 and September, 2013 and clinical efficacy was evaluated in 239 cases and safety in 329 cases. The median duration of progression-free survival, PSA progression-free survival and PSA response were 169 days (95%CI, 142-190), 197 days (95%CI, 169-267) and 385 days, respectively. The decrease in PSA level was observed in 125 cases (52.3%). Rate of PSA decline ＞50 and ＞25% were 18.4 and 43.1, respectively, and rate of PSA best response (PSA decline ＞ 50%) was 32.6%. Multivariate analysis demonstrated that long duration of prior CAB therapy, Estracyt○R - pretreatment PSA value and bone metastasis influenced progression-free survival significantly. Adverse events were observed in 127 cases (38.6%). The major adverse events were anorexia which was observed in 35 cases (10.9%), gastrointestinal disorders observed in 32 cases (9.7%), abnormal laboratory test values observed in 31 cases (9.4%) and gynecomastia observed in 16 cases (4.9%). These results suggest the clinical efficacy and safety of Estracyt○R for chemotherapy-naïve castration-resistant prostate cancer (CRPC), and Estracyt○R is regarded as one of the treatment options for patients with CRPC, especially for patients who had long duration of prior CAB therapy.

Enhancement of chemotactic response to sodium acetate in the nematode Caenorhabditis elegans.

In this study, we investigated the chemotactic response of a wild-type (N2) nematode (Caenorhabditis elegans) to a water-soluble attractant, sodium acetate, after pre-exposure to the chemical. The chemotactic response to 1.0 M sodium acetate of the non-exposed control nematodes was lower than that of the nematodes that were pre-exposed to 1.0 M sodium acetate for 90 min (p < 0.05). The increase in the response to sodium acetate was observed up to 6 hr, but not at 12 hr after exposure. To clarify the mechanism of this enhancement of the chemotactic response, several mutants were used. The chemotactic response of pre-exposed tph-1 and bas-1 mutants, whose main defect was serotonin secretion, was enhanced in comparison with that of the control mutants (p < 0.01). However, cat-1 and cat-2 mutants, which are respectively defective in serotonin and dopamine secretion and dopamine secretion only, showed no enhancement of the chemotactic response to sodium acetate, even when pre-exposed to this chemical. When the cat-1 and cat-2 mutants were pre-exposed to sodium acetate and bred in the presence of 40 mM dopamine, these mutants showed enhanced chemotactic response to sodium acetate (p < 0.05). These results suggest that the enhancement of chemotactic response to sodium acetate after pre-exposure to this chemical is modulated by dopaminergic neurotransmission.