Docetaxel and epirubicin compared with docetaxel and prednisone in advanced castrate-resistant prostate cancer: a randomised phase II study.

BACKGROUND: This randomised phase II study compared the activity and safety of the combination docetaxel (D)/epirubicin (EPI) with the conventional treatment D/prednisone (P) in advanced castrate-resistant prostate cancer (CRPC) patients. MATERIALS AND METHODS: Patients were randomly assigned to D 30 mg m(-2) as intravenous infusion (i.v.) and EPI 30 mg m(-2) i.v. every week (D/EPI arm), or D 70 mg m(-2) i.v. every 3 weeks and oral P 5 mg twice daily (D/P arm). Chemotherapy was administered until disease progression or unacceptable toxicity. RESULTS: A total of 72 patients were enrolled in the study and randomly assigned to treatment: 37 to D/EPI and 35 to D/P. The median progression-free survival (PFS) was 11.1 months (95% CI 9.2-12.6 months) in the D/EPI arm and 7.7 months (95% CI 5.7-9.4 months) in the D/P arm (P=0.0002). The median survival was 27.3 months (95% CI 22.1-30.8 months) in the D/EPI arm and 19.8 months (95% CI 14.4-24.8 months) in the D/P arm (P=0.003). Both regimens were generally well tolerated. CONCLUSION: The treatment of advanced CRPC with weekly D combined with weekly EPI was feasible and tolerable, and led to superior PFS than the treatment with 3-weekly D and oral P.

Priapism due to sacrococcygeal chordoma metastasis treated with radiation therapy.

We are reporting the first case of priapism due to a sacrococcygeal chordoma metastasis treated with radiation therapy as palliative treatment.

The use of RT-"nested" PCR of prostate specific antigen to detect hematogenous neoplastic cells in patients with prostate adenocarcinoma.

The aim of this study was to determine the presence of hematogenous neoplastic cells in patients with prostate cancer. We used a reverse transcription (RT) "nested" polymerase chain reaction (PCR) of prostate-specific antigen (PSA) mRNA to detect the presence of circulating tumor cells in 52 patients who underwent radical prostatectomy with lymphadenectomy. Blood samples were obtained before and after the surgical manipulation. Seven (13.5%) preoperative samples presented evidence of circulating neoplastic cells. All postoperative specimens studied presented a negative result at analysis 24 h after surgical manipulation. Although we did not find a statistical correlation between the PSA-PCR results and clinical-histopathological parameters, the presence of circulating prostate cells was strongly correlated with an elevated Gleason score of primary tumor (P<0.01). Thus our data show the positive effect of surgical treatment in removing the metastases source. The sensitive RT-nested PCR assay may play a crucial role in the administration of adjuvant therapy of patients with prostate adenocarcinoma.

Sildenafil does not improve sexual function in men without erectile dysfunction but does reduce the postorgasmic refractory time.

Sildenafil is one of two oral drugs approved for first-line treatment of erectile dysfunction (ED). Anecdotally, some young healthy men who wish to enhance their sexual performance are requesting or abusing sildenafil. In this randomized double-blind, placebo-controlled clinical study, we investigated the effect of sildenafil in young men without ED. A total of 60 young healthy men age 20-40 y with no reported ED were enrolled for this single-dose home-use study. Subjects had used no medication in the 6 months prior to the study. All had been engaged in a stable relationship for at least 3 months. After completing the IIEF-5 questionnaire, patients were randomized in a double-blind fashion to receive either one 25 mg tablet of sildenafil (group 1) taken prior to intercourse, or an identical placebo tablet (group 2). All subjects completed a questionnaire relating to their erectile quality. There were no differences between the two groups in the reported improvement of erection quality, 12/30 sildenafil vs 10/30 placebo (Fisher's test, P=0.79). Sildenafil caused a significant reduction of the postejaculatory refractory time (12/30 vs 4/30) (chi(2) test, P=0.04). Sildenafil does not improve erections in young healthy men. Sildenafil should not be given to young healthy men to improve their erections and patients should be advised against recreational abuse of the drug. In this limited single-dose home study, sildenafil appears to reduce the postorgasmic refractory time. Although controlled studies are needed to evaluate the efficacy of erection-enhancing drugs in premature ejaculation, it is possible that sildenafil might be useful for this indication.

Penile length is normal in most men seeking penile lengthening procedures.

Concerns over penile size and a desire for a longer penis are common in the male population. The number of male patients seeking an andrological consultation for the problem of 'short penis' is increasing. We looked at the numbers of patients presenting to a University andrology clinic over a 2-y period and correlated their perceived penis size with the accepted norms. Sixty-seven patients were evaluated with a median age of 27 (range 16-55) complaining of 'short penis' and requesting surgical correction. Clinical history, including the IIEF-5 questionnaire and an accurate physical examination were obtained. Data concerning measures of penile length and circumference were recorded in both the flaccid and fully stretched states and compared to the normal reference range as previously described in the nomogram we recently published (Eur Urol 2001; 39: 183-186.). All patients were also asked to estimate the length of a normal sized penis.Fourty-four (65.7%) complained of a short penis only while flaccid, 22 patients (32.8%%) while both flaccid and erect, and only one patient (1.5%) was worried only by the erect length of the penis. Fifteen (22.4%) also complained about their penile circumference. Fifty-seven (85%) patients thought a 'normal' penile length should range from 10 to 17 cm (median value of 12 cm). Ten patients (15%) were not able to estimate 'normal' penile size. No patient was found to have a penile length under the 2.5 percentile according to our nomogram. Forty-two (62.7%) subjects recalled the problem starting in childhood, when they felt that their penis was smaller than their friends'. In 25 patients (37.3%) the problem started in the teenage years after seeing erotic images. Our data show that most men who seek penile lengthening surgery overestimate 'normal' penile length. In our series, none of the patients could be classified as having a severely short penis according to our nomogram and none had any anatomical penile abnormality. Most found the use of a nomgram to show them how they compared with other men helpful. We suggest that documentation of such a demonstration should be made for any man seeking an opinion on penile lengthening surgery.

Cyclophosphamide, epidoxorubicin and Carboplatin as treatment for advanced-carcinoma of the bladder - a phase-ii study.

In advanced carcinoma of the bladder, the M-VAC chemotherapy schedule can yield positive results, but at the cost of very high toxicity. Recent studies have shown epidoxorubicin and to a lesser degree, carboplatin to be active against urothelial tumors, with cardiac, haematological and renal toxicity lower than that observed with CISCA or M-VAC chemotherapy regimens. In this study, we determined the toxicity and efficacy of cyclophosphamide 400 mg/m(2), epidoxorubicin 75 mg/m(2) and carboplatin 300 mg/m(2) in a 28-day course. From February 1990 to December 1991, we enrolled 33 advanced bladder cancer patients (25 males, 8 females), mean age 63 years. 31 patients were evaluable for toxicity and response. The major disease localizations were: locoregional 15 (48%), lymph nodes 6 (20%), liver 5 (16%), lung 3 (10%) and bone 2 (6%). A total of 186 cycles of therapy were administered, with a mean of 5.4 per patient. Six patients (19%) had a complete response (CR): 2 locoregional, 3 lymph node and 1 lung. Eleven patients (36%) had a partial response (PR), for an overall response rate of 55%. The median duration of response was 53 weeks and median survival for the entire group of patients was 40 weeks. No delays or interruptions due to sepsis occurred during therapy; haematological, cardiac and renal toxicity were below WHO grade 3. The efficacy of this chemotherapy regimen proved to be comparable to that of more aggressive schedules, while its toxicity was markedly lower.

The role of the detection of hematogenous micrometastasis in prostate adenocarcinoma and malignant melanoma by RT-PCR.

Recent studies reported the possibility of detecting prostate adenocarcinoma and malignant melanoma cells in peripheral blood using RT-PCR of prostatic specific antigen (PSA), prostatic specific membrane antigen (PSMA) and Tyrosinase mRNAs. The PCR results showed high variability, ranging between 0% and 100% of positivity in patients with advanced disease. Our purpose was to evaluate the presence of tumor marker mRNAs in peripheral blood of prostate cancer and melanoma patients by means of RT-nested-PCR. We tested 70 and 36 peripheral blood samples from prostate carcinoma and malignant melanoma patients, respectively. The RT-PCR analysis showed the presence of PSA cDNA in 9 out of 70 (12.9%); PSMA cDNA in 14 out of 70 (20%); and Tyrosinase cDNA in 2 out of 36 (5.5%) peripheral blood samples from melanoma patients. Our study confirms the applicability of this sensitive method to monitor disease status. Although, the RT-nested-PCR of Tyrosinase is able to detect neoplastic cells in peripheral blood specimens, we suggest the necessity of a great caution in interpreting PCR results when the nested method has been used.

Endoluminal instillation of epidoxorubicin as adjuvant treatment for upper urinary tract urothelial tumours.

Intravesical use of chemotherapeutic agents has been documented as effective and beneficial in the treatment and prophylaxis of bladder urothelial cancer. Because of the success achieved with these agents, several investigators have proposed these same drugs as adjuvant treatment after conservative procedures for urothelial tumours of the upper urinary tract. Experiences concerning topical therapy for upper tract urothelial neoplasms are still limited, but suggest a great potential benefit in terms of improved tumour control. Advances in endourologic techniques and increasing interest in the conservative management of upper urinary tract urothelial cancer may lead to more frequent use of topical chemotherapy. Specific guidelines and surveillance protocols, similar to those with superficial bladder cancer, are required to determine the role of this adjuvant therapy in the treatment of urothelial tumours of the upper urinary tract. This report shows our experience gained on endoluminal instillation of epidoxorubicin in a selected group of 9 patients who underwent local excission of ureteral or renal pelvis tumours.

Gemcitabine plus Epi-doxorubicin as first-line chemotherapy for bladder cancer in advanced or metastatic stage: a phase II.

Combination chemotherapy with newer, more active drugs in patients with advanced and/or metastatic bladder cancer might show improved response rate and survival. Gemcitabine (GEM) and Epidoxorubicin (EPI) have demonstrated activity in this disease. In addition, experimental studies in vitro have shown that the two agents have additive-synergistic effects when used in combination. Our prior phase I dose-finding study in previously untreated patients with advanced or metastatic bladder cancer defined recommended doses for further trials of GEM 1000 mg/m2 and EPI 25 mg/m2 on days 1, 8 and 15 every 28 days. A phase II trial at this dose level was initiated in previously untreated patients to assess efficacy and toxicity. Eligible patients had measurable disease; Karnofsky performance status (PS) of > 40; no prior chemotherapy; and adequate bone marrow reserve, cardiac, hepatic and renal function. Thirty- one patients (22 males, 9 females) with median age of 64 (range 44-75) and median PS of 80 were accrued, and all were eligible. Twelve patients had T4N1-2 M0, 8 had lymph node only metastases, while 11 had visceral metastases (liver, bone, lung). A total of 181 cycles was administered (range 3-7 per patient). Major toxicities (WHO grade > or = 3) were: neutropenia in 5 patients, thrombocytopenia in 2 patients, and anemia in 2 patients. Three patients had febrile neutropenic episodes and only 3 patients required dose reduction. Grade 1-2 non-hematological toxicities included nausea/vomiting, stomatitis and alopecia. No cardiac toxicity was observed. Of the 30 response evaluable patients, 17 (57%) demonstrated a major response (3 complete and 14 partial) (95% CI: 39%-75%), 7 had stable disease (23%) and 6 progressed (20%). These preliminary results confirm the phase I observation that the combination of GEM--EPI is highly active in the treatment of advanced and metastatic bladder cancer with a favourable toxicity profile.

Melatonin as biological response modifier in cancer patients.

The neuroendocrine system modulates the immune response through neuropeptides and neurohormones, findings which point to the existence of a neuro-endocrine-immune system regulatory axis. At the same time, there is growing evidence that the pineal gland has anti-neoplastic properties, which include the action of its principal hormone, melatonin (MLT), on the immune system through the release of cytokines by activated T-cells and monocytes. The present study was carried out on 31 patients (19 males and 12 females, age range 46-73 years) with advanced solid tumors (7 gastric, 9 enteric, 8 renal, 5 bladder, 2 prostate) who either failed to respond to chemotherapy and radiotherapy or showed insignificant responses and were therefore shifted to MLT therapy (10 mg/die orally for 3 months). We obtained blood samples just before the start of MLT administration and after 30 days of therapy. Plasma was collected in EDTA tubes on ice, immediately centrifuged at 4 degrees C and stored frozen at -80 degrees C; samples were measured by immunoradiometric assays (Medgenix-Fleurus, Belgium) for tumor necrosis factor alpha (TNF), interleukin-1, 2 and 6 (IL-1, IL-2, IL-6) and interferon gamma (IFN). We used Student's paired t-test to compare each patient's cytokine circulating levels before and after MLT administration and found a significant differences (p < 0.05). After 3 months of therapy, none of our patients displayed adverse reactions to MLT or had to discontinue treatment. Nineteen patients (61%) showed disease progression. The other 12 (39%), however, achieved disease stabilization with no further growth of either the primary tumor or of secondaries; moreover, they experienced an improvement in their general well-being, in terms of Tchekmedyian's criteria, associated with a significative decrease of IL-6 circulating levels. These findings are consistent with the hypothesis that MLT modulates immune function in cancer patients by activating the cytokine system which exerts growth-inhibitory properties over a wide range of tumor cell types. Furthermore, by stimulating the cytotoxic activity of macrophages and monocytes, MLT plays a critical role in host defence against the progression of neoplasia.

Weekly epidoxorubicin therapy in hormone-refractory metastatic prostate cancer.

In a pilot trial, we treated thirty-three hormone resistant metastatic prostate cancer patients with a combination of androgen blockade plus weekly cytotoxic therapy and determined both response and toxicity in 32 of them. Their median Karnofsky performance status at the time of entry was 65. We administered Epidoxorubicin (EpiDx) intravenously, at a dose of 35 mg/m2, every week for 4 months. Initially, all patients had only hormonal therapy and chemotherapy was added once they progressed. In terms of W.H.O. criteria, 9 patients (28%) had a partial response, the disease was stable in 14 (44%), and progressive in 9 (28%); even in this last group, 6 patients with bone metastases experienced lasting relief from pain. No patients had to interrupt treatment due to leukopenia or cardiotoxicity. Other toxicities, including nausea and vomiting, mucositis and alopecia, were mild. Pretreatment prostate-specific antigen (PSA) levels decreased significantly (p < 0.05) in 26 patients (81%) after treatment. In our view, weekly EpiDx administration serves as an active regimen in hormone-refractory prostate cancer.

The role of lomefloxacin in the treatment of chronic prostatitis.

The choice of antimicrobial agents for treatment of prostatitis should be based on two factors: in vitro sensitivity of isolated pathogens and potential intraprostatic penetration of the molecule. Unfortunately, only a few antibiotic agents penetrate prostatic fluid which is the primary site of infection. Lomefloxacin, a once-daily difluoroquinolone, could play a central role in the therapy of prostatitis because it has sufficient liposolubility, low ionization (pKa), low protein binding, small molecular size, long serum elimination half-life and it can pass from interstital fluid across prostatic cells into the lumen. This study was carried out on 12 patients (mean age 65 years) with normal hepatic and renal function, divided into two groups of 6 subjects each. Lomefloxacin was administered for perioperative antisepsis at the dose of 400 mg orally once a day for 4 days. Serum and tissue were sampled in the two groups of patients 4 h (Group A) and 8 h (Group B) respectively after the last drug administration. Tissue penetration was higher than serum, with a T/S >2 in the prostatic capsule and seminal blister, and a T/S >1.6 in the adenomatous tissue, in both groups of patients. In addition, the prostatic tissue concentrations exceeded the MIC for the main pathogens usually involved in urogenital infections. Therefore, because of its pharmacokineitic and pharmacodynamic characteristics, lomefloxacin is proposed as an efficacious therapeutic option, even for the treatment of chronic prostatitis.

[Posttraumatic functional exclusion of the kidney of nonvascular origin. Description of a case and review of the literature]. / Esclusione funzionale post-traumatica del rene da causa non vascolare. Descrizione di un caso e revisione della letteratura.

A review of published series about 56 cases with unilateral nonvisualization on excretory urography after external trauma have been described: the renal injury causing the nonvisualization was contusion in 8 patients, laceration in 13, rupture in 12 and renal pedicle in 19. The acquisition of the most important methods has allowed a total view as about minimal lesions (contusion, laceration), as rupture or fragmentation of the kidney and renal pedicle. We have evaluated 32 cases of renal traumatic injuries and we have studied one case with unilateral nonvisualization stressing the diagnostic, etiopathogenetic and therapeutic problems.

[Andrologic pathology discovered druing conscription screening: how many young men were unaware?]. / Patologia andrologica rilevata in corso di visita di leva: quanti giovani ne erano a conoscenza?

BACKGROUND: In Italy the visit during conscription is a valid instrument for epidemiologic research. The aim of this study was to evaluate the incidence of andrologic diseases in a population of 18 years old young Italian men and to estimate in how many of them it was a first diagnosis. METHODS: This randomized study was conducted during 1998 at the Military District of Florence where an andrological visit was performed on 11,649 young men living in Tuscany. An evaluation of external genitals and secondary sexual characters was made. All the visits were performed by the same doctor. They were requested to specificity if they were familiar with the professional figure of the andrologist. RESULTS: Some andrological disorders were found in 3892 (33.4%) of them and in 3469 (89.2%) it was the first diagnosis. Only 3.7% knew the role of the andrologist and 70% didn't know where to apply for their problems. CONCLUSIONS: The results of this study showed a poor familiarity with the figure of the andrologist even though about 1/3 of them should be treated for an andrologic disease which is often undiagnosed. It is personal opinion that these results should make us to think about the consequences that the abolition of male conscription may have given that, for many young Italians, the medical check-up for military service is the first, and often the last, occasion for a control of the genital system.

[The post-adenomectomy dysuria-hematuria syndrome]. / La sindrome disurico-ematurica post-adenomectomia.

The dysuria syndrome consists of the persistence or accentuation following adenomectomy of the symptoms which caused the patient to seek the urologist's advice. It is frequent event whose causes are largely connected to physiopathological events which are also influenced by the developing role between the urologist and patients in view of prostate disease. The authors analyse the various causes of post-adenomectomy dysuria and emphasise the importance of a precise diagnosis and the correct indications for surgery for the prevention of this disease.

Real-time elastography in the diagnosis of prostate tumor.

AIM: To assess the diagnostic gain of transrectal real-time elastography (RTE) compared to transrectal B-mode ultrasonography (US) in the detection of tumors in patients suspected of having prostate cancer. MATERIALS AND METHODS: Eighty-four patients suspected of having prostate cancer on the basis of clinical and biochemical evaluation underwent transrectal US, RTE and transperineal prostate biopsy. RESULTS: Biopsy was considered the gold standard. Analysis related to the total number of patients showed a B-mode US sensitivity of 56%, specificity 80%, positive predictive value (PPV) 70% and negative predictive value (NPV) 67%. Analysis related to the total number of biopsy cores showed sensitivity 33%, specificity 92%, PPV 69% and NPV 73%. In the patient-related analysis, RTE sensitivity was 51%, specificity 75%, PPV 64% and NPV 64%, while the core-related analysis showed sensitivity 36%, specificity 93%, PPV 72% and NPV 74%. Comparison of B-mode US and RTE diagnostic accuracy in the detection of tumors located in the peripheral zone of the prostate gland showed a significant difference. Analysis related to the total number of biopsy cores harvested in the peripheral zone of the prostate gland showed a B-mode US sensitivity of 48%, specificity 81%, PPV 75% and NPV 58%, whereas RTE achieved the following values: sensitivity 66%, specificity 78%, PPV 77%, and NPV 67%. CONCLUSIONS: RTE is a valid addition to B-mode US, and RTE reached a higher accuracy than B-mode US in the evaluation of the peripheral zone of the prostate gland and in the selection of appropriate biopsy sites.

Weekly paclitaxel and epirubicin in the treatment of symptomatic hormone-refractory advanced prostate carcinoma: report of a phase II trial.

The efficacy of weekly paclitaxel in androgen-independent prostate cancer and its addictive cytotoxicity with anthracycline derivatives led us to determine the safety and efficacy of a weekly schedule of paclitaxel and epirubicin. Between October 2000 and November 2002, 32 patients were enrolled in this study. Patients characteristics included a median age of 72 years (range 68-77), adequate hepatic, cardiac, renal and bone marrow functions, ECOG performance status of 1-2, and no prior chemotherapy. All patients had received hormonal manipulation and seven patients (22%) had received prior palliative radiation therapy. The regimen consisted of paclitaxel 70 mg/m2 i.v. infusion for 2 h and epirubicin 30 mg/m2 in bolus every week. Treatment was continued for 3 months or until disease progression or unacceptable toxicity were observed. During the study, prostate-specific antigen (PSA) was monitored and response was defined as a 50% reduction in PSA levels, to be confirmed 4 weeks later. Thirty-one patients were evaluable for toxicity and 21 for objective response. Seventeen patients (57%) had a decline above 50% in PSA level that lasted more than 4 weeks with a median time to PSA progression and a median duration of PSA response of approximately 5.5 months. Ten of the 21 patients with measurable disease (47%) had a confirmed objective response (one complete response and 20 partial responses). Thirteen of 25 symptomatic patients (56 %) had improvement in pain. The median time to disease progression was 7.6 months and the median survival was 12.9. The most prominent grade 3 toxicities were reversible myelosuppression and fatigue. Nausea, vomiting, diarrhea and peripheral edema were minimal. No evidence of cardiac toxicity was recorded. Alopecia was frequent, but reversible, in all patients. We conclude that despite the small sample size, this study demonstrates that the combination of weekly paclitaxel and epirubicin is a well-tolerated regimen for androgen-independent prostate cancer. The results imply that a combination of these agents in a weekly schedule may have clinical potential in prostate cancer treatment.