A 5-year retrospective analysis of 5α-reductase inhibitors in men with benign prostatic hyperplasia: finasteride has comparable urinary symptom efficacy and prostate volume reduction, but less sexual side effects and breast complications than dutasteride.

OBJECTIVE: We evaluated 5-year safety, efficacy and prostate volume data from BPH patients treated with finasteride or dutasteride. METHODS: A retrospective analysis of 378 consecutive men treated with 5α-reductase inhibitor monotherapy between January 2004 and September 2009 (197 on finasteride and 211 on dutasteride) in a single clinic was performed. Efficacy assessments included International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), postvoid residual urine volume (PVR), prostate-specific antigen (PSA) and prostate volume (PV). Safety assessments included International Index of Erectile Function (IIEF) and adverse events. Patients were evaluated at 3 months, 1 year and yearly thereafter. RESULTS: Mean age of the group was 58.7 ± 6.7 years. Maintenance of therapy at 5 years was 57.4% and 42.5% for the finasteride and dutasteride groups respectively. Changes in IPSS, Qmax, PVR, PV and PSA were similar for both groups at 5 years. The incidence of erectile dysfunction, ejaculatory dysfunction and decreased libido resulting in discontinuation from therapy was significantly (p < 0.01) higher in the dutasteride (5.1%, 2.4%, 2.7% respectively) compared with the finasteride (2.1%, 1.8%, 1.4% respectively) group. In addition, the incidence of self-reported breast tenderness and/or enlargement was significantly (p < 0.01) greater in the dutasteride (3.5%) compared with the finasteride (1.2%) group. CONCLUSIONS: In this retrospective analysis of data from consecutive patients treated at a single clinic, both finasteride and dutasteride were effective therapies for the management of lower urinary tract symptoms. However, dutasteride resulted in significantly more sexual side effects and breast complications than finasteride.

Prodrugs of anthracyclines in cancer chemotherapy.

Designing and developing truly tumor-specific prodrugs remains a challenge in the field of cancer chemotherapy. Active targeting strategies, on the one hand, aim at exploiting membrane-associated receptors or antigens for drug delivery; on the other hand, the enhanced vascular permeability and retention of macromolecules in tumor tissue substantiates the concept of passive targeting. Consequently, research efforts have concentrated on conjugating anticancer agents with a wide spectrum of carriers including antibodies, peptides, serum proteins, and synthetic polymers. Conversely, low-molecular weight prodrugs of anticancer agents have been developed that do not bear an active or passive targeting moiety, but are activated by tumor-associated enzymes at the tumor site. Anthracyclines probably represent the class of anticancer agents that has been most widely used for the development of prodrugs. This overview gives an update of the various low- and high-molecular weight prodrugs of anthracyclines, e.g. with antibodies, peptides, carbohydrates, serum proteins or synthetic polymers, that have been developed over the past 20 years and that exemplify the salient features of a respective drug delivery system. A detailed description will be dedicated to anthracycline prodrugs that have reached an advanced stage of preclinical testing or that have entered clinical trials.