Tadalafil Preferred to Sildenafil As Treatment for Erectile Dysfunction

RESEARCH HIGHLIGHTS

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GLOSSARY In all, six patients fulfilled the trial endpoint onset of activity, while those taking tadalafil INTERNATIONAL INDEX of freedom from disease progression at were advised to take the drug between 12 h OF ERECTILE FUNCTION (IIEF) 6 months; this number was insufficient to and 30 min before sexual activity, and that the A 15-item, self-administered show that treatment had any effect. Of 47 effects could last for up to 24 h. questionnaire specifically evaluable patients, 1 had a partial response Both drugs were well tolerated, with few used for the assessment of male erectile function; and 19 had stable disease followed by disease patients reporting adverse effects. Of the six questions (1–5, 15) are progression (median duration 5.1 months). The patients who completed both treatments, related to erectile function; three (6–8) to satisfaction authors concluded that carboxyamidotriazole 29% chose sildenafil and 71% chose tadalafil with intercourse, two (9, 10) had minimal to no activity. for the extension period. For both treatments, to orgasm, two (11, 12) to sexual desire and two Median survival, however, was 12.5 months— large improvements from the baseline were (13, 14) to overall comparable to that expected for newly diag- recorded in the IIEF scores and SEP diary. satisfaction nosed patients with RCC. Advanced RCC Jim Casey SEXUAL ENCOUNTER can be an indolent disease in some patients, Original article Eardley I et al. (2005) An open-label, PROFILE (SEP) A diary with seven questions and those who have adequate organ func- multicentre, randomized, crossover study comparing that enables patients to tion and performance status (and are thus sildenafil citrate and tadalafil for treating erectile dysfunction record sexual events in men naïve to phosphodiesterase 5 inhibitor therapy. BJU eligible for clinical trials of second-line treat- Int 96: 1323–1332 ments) have a more prolonged survival than previously thought. Caroline Barranco

Original article Dutcher JP et al. (2005) Phase II study Tumor grade and EGFR of carboxyamidotriazole in patients with advanced renal expression predict disease stage cell carcinoma refractory to immunotherapy. Cancer 104: in urine ThinPrep® specimens 2392–2399 Politi and colleagues in Greece investigated the expression of epidermal growth factor Tadalafil preferred to sildenafil receptor (EGFR) and proliferating cell nuclear as treatment for erectile antigen (PCNA) in ThinPrep® (Cytyc Corp., dysfunction Boxborough, Massachusetts) urine samples and tissue sections from 42 patients with newly An open-label, crossover study conducted by diagnosed bladder cancer. Their aim was to Eardley et al. in the UK and Italy compared the determine the predictive value of these markers effect of two phosphodiesterase-5 inhibitors, in bladder cancer staging. sildenafil and tadalafil, on the treatment of erec- Patients were divided into two groups accord- tile dysfunction. After a 4-week pretreatment ing to clinical stage. Patients in the muscle assessment, 367 men were randomized in a invasive (MI) group (n = 24) had a clinical stage 1:1 ratio to receive sildenafil for 12 weeks fol- of T≥2, whereas patients with a clinical stage of lowed by tadalafil for 12 weeks, or vice versa, Tα or T1 (n = 18) were classified as nonmuscle- with a 7–10-day washout period between invasive (NMI). treatments. Patients could choose to alter ThinPrep® processed urine samples and the treatment dose during the first 8 weeks of bladder biopsy tissue sections were pretreatment in each period. After the completion pared, and immunocytochemical and immuno- of both 12-week periods and a 4-day washout histochemical studies were performed by period, patients chose which treatment and an automated immunostainer using EGFR dose to follow during an 8-week extension. and PCNA primary antibodies, along with Effectiveness of treatment was assessed by appropriate positive and negative controls. the IIEF scores and the SEP diary. When the immunocytochemistry results Sildenafil and tadalafil differ in their pharmaco- from the ThinPrep® slides were compared to kinetics. The absorption of sildenafil is affected the immunohistochemistry results from the by high-fat foods, while tadalafil is unaffected. tissue sections, a striking concordance was Tadalafil has a half-life of 17.5 h, while for seen in the immunopositivity status of EGFR sildenafil the half-life is 4–5 h. Patients taking and PCNA, as well as in the percentage of sildenafil were therefore informed that the dose immunoreactive cells. could be taken between 4 h and 30 min before Univariate analysis revealed that both the sexual activity, and that food could affect the grade of malignancy and EGFR expression

68 NATURE CLINICAL PRACTICE UROLOGY FEBRUARY 2006 VOL 3 NO 2