Comparison of two adjuvant hormone therapy regimens in patients with high-risk localized prostate cancer after radical prostatectomy: primary results of study CU1005.

The role of adjuvant hormonal therapy and optimized regimens for high-risk localized prostate cancer after radical prostatectomy remains controversial. Herein, the clinical trial CU1005 prospectively evaluated two regimens of maximum androgen blockage  or bicalutamide 150 mg daily as immediate adjuvant therapy for high-risk localized prostate cancer. Overall, 209 consecutive patients were recruited in this study, 107 of whom received 9 months of adjuvant maximum androgen blockage, whereas 102 received 9 months of adjuvant bicalutamide 150 mg. The median postoperative follow-up time was 27.0 months. The primary endpoint was biochemical recurrence. Of the 209 patients, 59 patients developed biochemical recurrence. There was no difference between the two groups with respect to clinical characteristics, including age, pretreatment prostate-specific antigen, Gleason score, surgical margin status, or pathological stages. The maximum androgen blockage group experienced longer biochemical recurrence-free survival (P = 0.004) compared with the bicalutamide 150 mg group. Side-effects in the two groups were similar and could be moderately tolerated in all patients. In conclusion, immediate, 9-month maximum androgen blockage should be considered as an alternative to bicalutamide 150 mg as adjuvant treatment for high-risk localized prostate cancer patients after radical prostatectomy.

Effect of carrageenan on poloxamer-based in situ gel for vaginal use: Improved in vitro and in vivo sustained-release properties.

The aim of this work is to explore effects of carrageenan on sustained-release properties of poloxamer 407-based vaginal in situ gel. After formulation of composite gel systems composed of carrageenan and poloxamer 407, in vitro release profiles and in vivo local drug residence after vaginal administration in mice was investigated using acyclovir as the model drug. Rheological experiment was conducted to investigate effects of carrageenan on temperature-dependent viscoelasticity of poloxamer 407-based gels. It appeared that carrageenan and poloxamer 407 could form composite gel systems with good thermosensitity similar to gels containing only poloxamer 407. In the in vitro release experiment, carrageenan significantly decreased the release rate of acyclovir, retarded the dissolution of poloxamer 407 and slowed the gel erosion (weight loss) in a concentration-dependent manner. In vivo local drug residence experiment indicated that carrageenan significantly prolonged local residence of acyclovir and further showed a synergistic bioadhesive effect with acrylic acid polymers (Carbopol). In conclusion, carrageenan was able to improve the sustained-release properties of poloxamer 407-based in situ gel, indicating that the combination of carrageenan and poloxamer 407 may find use in the development of vaginal in situ gel drug delivery systems with prolonged local residence and thus better clinical outcome.