Real-world experience of abiraterone acetate plus prednisone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: long-term results of the prospective ABItude study.

BACKGROUND: Limited real-world data exist on the effectiveness and safety of abiraterone acetate plus prednisone (abiraterone hereafter) in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) naive to chemotherapy. Most of the few available studies had a retrospective design and included a small number of patients. In the interim analysis of the ABItude study, abiraterone showed good clinical effectiveness and safety profile in the chemotherapy-naive setting over a median follow-up of 18 months. PATIENTS AND METHODS: We evaluated clinical and patient-reported outcomes (PROs) of chemotherapy-naive mCRPC patients treated with abiraterone as for clinical practice in the Italian, observational, prospective, multicentric ABItude study. mCRPC patients were enrolled at abiraterone start (February 2016-June 2017) and followed up for 3 years; clinical endpoints and PROs, including quality of life (QoL) and pain, were prospectively collected. Kaplan-Meier curves were estimated. RESULTS: Of the 481 patients enrolled, 454 were assessable for final study analyses. At abiraterone start, the median age was 77 years, with 58.6% elderly patients and 69% having at least one comorbidity (57.5% cardiovascular diseases). Visceral metastases were present in 8.4% of patients. Over a median follow-up of 24.8 months, median progression-free survival (any progression reported by the investigators), time to abiraterone discontinuation, and overall survival were, respectively, 17.3 months [95% confidence interval (CI) 14.1-19.4 months], 16.0 months (95% CI 13.1-18.2 months), and 37.3 months (95% CI 36.5 months-not estimable); 64.2% of patients achieved ≥50% reduction in prostate-specific antigen. QoL assessed by Functional Assessment of Cancer Therapy-Prostate, the European Quality of Life 5 Dimensions 3 Level, and European Quality of Life Visual Analog Scale remained stable during treatment. Median time to pain progression according to Brief Pain Inventory data was 31.1 months (95% CI 24.8 months-not estimable). Sixty-two patients (13.1%) had at least one adverse drug reaction (ADR) and 8 (1.7%) one serious ADR. CONCLUSION: With longer follow-up, abiraterone therapy remains safe, well tolerated, and active in a large unselected population.

Sexual dysfunctions in multiple sclerosis.

AIM: The aim of this study was to analyze the sexual dysfunction in patients affected by multiple sclerosis. METHODS: From January 2005 to December 2007, 221 consecutive patients, 97 women and 124 men, were included in the study. Age range was 20+/-65 years (average 38.77). Fifty-two patients, 14 women (26.9%) and 38 men (73%), among those who have had sexual dysfunctions, showed their will to tackle their problem, and were thus taken into consideration by the Department of Andrology. Sexual activity of these patients has been estimated by self-administered questionnaire, through the International Index of Erectile Function (IIEF) for men and Index of Female Sexual Arousal (IFSA) for women. All 64 patients started a domiciliary therapy with sildenafil 50 mg, and in case of failure, sildenafil 100 mg. Results have been estimated for men according to the IIEF questionnaire and to the answers to the third and fourth question, concerning the capacity to have and keep an adequate erection during a sexual intercourse, and for women according to the IFSA questionnaire and to the answers given to questions number 1, 5, 6, and 10. RESULTS: Among the 124 male patients, 25 (20.1%) had a serious deficiency of the erectile function (score IIEF<10), 11 (8.8%) had a moderate deficiency (score from 11 to 16), and 20 (16.12%) had a light deficiency (score from 17 to 25). Twenty-five patients affected with serious erectile deficiency, also reported a contemporaneous decrease of libido. Among the 97 female patients, 22 (28.86%) of them reported a serious decrease of the genital sensitivity and of the sexual desire; 22 (22.68%) of them reported instead a serious decrease of the vaginal lubrication; 9 (9.2%) reported a moderate decrease of the sensitivity, and 10 (10.30%) reported a moderate decrease of the vaginal lubrication. According to Disability Scale Expanded Score 52 male patients showed a 2.6 mean score (range 1.5-7); 14 female patients showed a 2.9 mean score (range 3-6). The answers to IIEF questions number three and four, and to the IFSA questions number 1, 5, 6 and 10 reported the achievement and keeping of an adequate erection after a follow-up of 4 sexual intercourse, and lubrication and sensitivity during a sexual intercourse in all the cases analysed. CONCLUSION: Sildenafil has been effective and safe in the treatment of sexual dysfunctions for both sexes. In all analysed patients sexual deficiency was due to the neurological and central nervous system on which depend different dysfunctions correlated with the extension and the gravity of the multiple sclerosis. IIEF questions number 13 and 14 and IFSA questions number 21 and 22 showed a clear improvement of the sexual life quality of these patients, after sildenafil therapy.

Sexual dysfunction in patients under dialytic treatment.

AIM: Erectile dysfunction (ED) is very common in patients with renal failure, probably as a side effect of long-term treatments and dialysis, among other etiologic factors. Over the last few years, new highly effective oral treatments for ED have been introduced in the market. We designed a prospective trial in 42 dialytic patients with ED, focusing on the therapeutic effect of syldenafil and apomorphine. METHODS: Forty-two patients aged 57 years (range 34-71), [40 on hemodialysis (HD) and 2 on peritoneal dialysis (PD)] were enrolled in a prospective study comparing sildenafil with apomorphine. After a careful nephrologic anamnesis and uroandrological examination, all patients underwent, before and after each treatment, the International Index Erectile Function (IIEF) test, and the Life Satisfaction test. Expert opinion was based on grading of evidence based medical literature, widespread internal committee discussion, public presentations and debates. RESULTS: The 2 patients on PD were the only responders to 25 mg sildenafil; 25 patients on HD had a clear improvement of the IIEF score after 50 mg sildenafil administration; finally, 11 patients on HD would benefit only from 100 mg sildenafil; the nonresponders to sildenafil were only 4 patients, having to switch to PgE1. When apomorphine was tested on the same patients, a mild response was seen only in 6 patients at the 3 mg dose. No response was seen in the 2 patients on PD. CONCLUSIONS: There was a statistically significant difference in the therapeutic role of sildenafil versus apomorphine, the first producing an overall improvement of the IIEF in 90.5% of patients, compared to 14% of the same patients receiving apomorphine (P<0.001).

Compliance to longterm vasoactive intracavernous therapy.

From December 1986 to December 1991, 107 patients with organic impotence were advised to intracavernous pharmacological therapy with papaverine. Sixteen patients refused such treatment: 91 patients, after the determination of the therapeutical dose, underwent self injection. The follow up was 30-90 months. Thirty-seven patients (40.7%) withdraw the treatment within 3 months: 3 patients (3.3%) after losing the partner; 9 (9.9%) for intercurrent disease; 23 (25.3%) were unsatisfied for the therapy; 2 (2.2%) regained spontaneous erections. Complications were: local haematomas in 23 (42.6%); prolonged erections in 6 (11.1%); fibrotic changes of the corpora cavernosa in 9 patients (16.7%); liver enzymes changes in 2 (3.7%). The reasons for the low compliance to the intracavernous pharmacological therapy with papaverine were analysed.

Study of mepartricin possible interactions with antilipemic drugs. Controlled clinical trials in patients with benign prostatic hyperplasia.

In order to more throughly study mepartricin pharmacodynamic characteristics, 2 groups of 15 patients with BPH and coexistent lipid metabolism disorders were studied in conformity with a sequential experimental design during which also systemic-acting (procetofen) and endoluminal-acting (cholestyramine) fat-lowering drugs were tried. The data obtained confirmed mepartricin specific effect on symptomatology and function in BPH and demonstrated the absence of positive and/or negative pharmacological interactions between the substance in question and the fat-lowering agents tried.

[Ultrasonically guided biopsy of the prostate for the diagnosis of carcinoma]. / La biopsia ecoguidata della prostata per la diagnosi di carcinoma.

Echoguided biopsy of the prostate is a new method used in the diagnosis of carcinoma. False negatives, which range between 7% and 27% of transperineal biopsies, can be reduced to 11% using ultrasound control. In 50% of cases carcinoma are located in the hypoechogenic area, in 45% in mixed echogenic areas and in 5% in hyperechogenic areas. The diagnosis of carcinoma was performed in 40.7% of patients examined. In conclusion, this method is shown to be a valuable and advisable aid.

[La Peyronie's disease: anatomical and functional evaluation using color Doppler echography]. / Malattia di La Peyronie: valutazione anatomica e funzionale con ecocolor Doppler.

We performed color duplex ultrasound in patients with Peyronie's disease in order to define the anatomy of corpora cavernosa and penile vascular abnormalities. We evaluated 20 patients, affected by Peyronie's disease, using echo-color-doppler after pharmaco-injection of PGE1 and autostimulation. We find that impotent patients had decreased EDV after 30 Minutes and after autostimulation; all patients had a normal PSV. The echo-colo-doppler is a useful tool in the evaluation of the penile vasculature, in patients with Peyronie disease, for its high sensitivity, low invasiveness, and good acceptance from patients. The results of this test could safely guide the therapeutic choice.

[Echo-guided biopsy of the transitional zone in the diagnosis of prostatic carcinoma]. / La biopsia ecoguidata della zona di transizione nella diagnosi di carcinoma prostatico.

Approximately 24% of prostate cancer originate in transition zone. To define the indications for transition zone biopsies from April 1994 to February 1996 we evaluated 112 men ranging in age from 56 to 84 years (mean 67.4). 94 patients presented elevated PSA levels and normal rectal examination (24 with negative prior systematic sextant biopsies). A group included 6 patients with palpable nodularity and normal PSA levels. A third group consisted of 12 men with sonographic abnormalities. Of the 112 patients evaluated 38 (34%) were found to have cancer on the prostate biopsies and 7 (18%) were positive only in sample of transition zone biopsies. We conclude that transition zone biopsies don't substantially improve the cancer detection rates in patients with palpable nodularity or sonographic abnormalities but are useful in patients with elevated PSA levels and/or negative prior systematic sextant biopsies.

[Preoperative staging of prostatic carcinoma: evaluation of the role of transrectal echography]. / Stadiazione preoperatoria del carcinoma prostatico: valutazione del ruolo dell'ecografia transrettale.

Radical Retropubic Prostatectomy (RRP) is the choice treatment for localized prostate cancer. Transrectal ultrasonography (TRUS) was used to predict local tumor extension in ninety-one patients prior RRP. In these patients 41% showed histologic evidence of extracapsular spread. These data suggest that ultrasonography is associated with considerable staging errors when used to evaluate men with clinically localized prostate cancer.

[Role of expectant therapy in prostatic carcinoma of low grade and staging]. / Ruolo della expectant therapy nel carcinoma della prostata di basso grado e stadio.

Low stage and grade prostate cancer can be treated by radical prostatectomy, radiotherapy and expectant therapy. Preoperative evaluation with biopsy is in many cases unreliable to pathological stage and grade. In this study we considered 31 patients with prostate cancer, evaluated with directed ultrasound guided biopsy (15) or with sextant biopsy (16). Sextant biopsy showed better results. Grading was confirmed by radical prostatectomy specimen in 62.5%. The role of expectant therapy is then discussed.

Erectile dysfunction and alcohol intake.

The objective of this work is to evaluate in a selection of patients with erectile dysfunction the influence of alcohol consumption and the response to alcohol abstinence with and without sildenafil association. Materials and Methods. In a population of 150 consecutive patients with erectile dysfunction we studied 50 patients aged between 22 and 77 years (mean 56±14 SD). These 50 patients were divided into three different treatment groups and were screened for three different levels of alcohol risk with two questionnaires. All patients were evaluated with an International Index Erectile Dysfunction (IIEF) questionnaire before and after one month of treatment. RESULTS. The 50 patients included 14 patients with high alcohol risk, 34 patients with low alcohol risk and only 2 patients with no alcohol risk. After one month, 29 patients responded to the therapy, and 21 did not respond. The IIEF questionnaire presented a statistically significant difference between the different risk groups before and after treatment (p≤0.05). All the patients were examined with a penile Doppler Ultrasound. Only 10 of them had an abnormal diastolic peak velocity (PDV) and only 1 presented both pathologic systolic peak velocity (PSV) and PDV. These 11 patients did not respond to therapies and 10 of them were at high alcohol risk. The alcohol consumption risk was directly correlated with PDV (p=0.00001; R2=0.4). CONCLUSIONS. The results of this study demonstrated a significant relationship between alcohol consumption and erectile dysfunction. This underlines the important therapeutic issue of alcohol abstinence in treating patients with erectile dysfunction.

[Tadalafil versus sildenafil citrate in the treatment of ED:Italian patients' preferences and explanatory notes].

This is an open, multicentre, randomized, crossover study having the aim to evaluate the preference for sildenafil citrate or tadalafil in a population of Italian patients affected by ED, and to compare the efficacy and safety of these two drugs. MATERIAL AND METHODS. From October 2003 to November 2004, thirteen Italian centers enrolled ED patients (age >18) being in steady and naïve relation to ED treatment, both through PDE5 inhibitors and any other treatment option. These patients were randomized to sildenafil or tadalafil for 12 weeks, after which they were switched to the alternative treatment for a further 12 weeks. The preference was evaluated through the Treatment Preference Question (TPQ): "During this clinical trial you have taken tadalafil and sildenafil for the treatment of erectile dysfunction. Which medication do you prefer to take for the next 8 weeks of treatment?". Moreover, patients were asked to express their preference as "strong" or "moderate" and to answer some questions to clarify the reasons behind their preference. SEP and IIEF-EF questionnaires were used for a comparison of efficacy. RESULTS. 167 patients were enrolled, 144 of whom completed both treatment periods. On being asked the TPQ, 75% of patients (n=108) decided to continue treatment with tadalafil, in particular because it made it possible to have an erection many hours after taking the medication (first or second preference reason for 64.8% of patients), while 25% (n=36) preferred sildenafil (p=0.001). Both drugs improved the IIEF-EF and SEP scores compared to baseline, with a slightly but significantly greater improvement with tadalafil for both parameters. CONCLUSIONS. Tadalafil and sildenafil are both effective and well tolerated. Most of the patients prefer tadalafil thanks to the possibility of having sexual intercourse many hours after taking the medication.

Paroxetine in the treatment of premature ejaculation.

OBJECTIVE: To test the efficacy and the adverse effects of a new anti-depressant drug (paroxetine) in the treatment of premature ejaculation. PATIENTS AND METHODS: The study comprised 32 men (mean age 28 years) with premature ejaculation (14 of whom ejaculated before penetration) who were treated with paroxetine (20 mg orally each evening for 2 months). The study group excluded those with neurological and psychiatric disorders, urinary tract infections and drug or alcohol abuse. RESULTS: After about 14 days, the patients' symptoms improved and all patients reported a longer interval before ejaculation. The adverse effects were sleepiness in 19 patients (61%) and mild sensory confusion in 21 (68%), but only one had to withdraw from therapy. Three weeks after the end of therapy, the premature ejaculation recurred in 28 (90%) of the patients. CONCLUSIONS: These results indicate that paroxetine is an effective therapy for premature ejaculation. Further studies with different dosages are necessary to decrease the adverse effects and to prolong the efficacy.

Advanced prostate cancer follow-up with prostate-specific antigen, prostatic acid phosphatase, osteocalcin and bone isoenzyme of alkaline phosphatase.

We report our experience in the follow-up of 63 patients with advanced prostate adenocarcinoma. We used prostate-specific antigen and prostatic acid phosphatase in 27 patients; in 36 patients we evaluated osteocalcin and bone isoenzyme of alkaline phosphatase, two markers of bone metabolism which seem to be good markers in the follow-up of patients with bone metastases.