Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer.

PURPOSE: To determine whether tamoxifen or anastrozole prevents gynecomastia and breast pain caused by bicalutamide (150 mg) without compromising efficacy, safety, or sexual functioning. PATIENTS AND METHODS: A double-blind, placebo-controlled trial was performed in patients with localized, locally advanced, or biochemically recurrent prostate cancer. Patients (N = 114) were randomly assigned to either bicalutamide (150 mg/d) plus placebo or in combination with tamoxifen (20 mg/d) or anastrozole (1 mg/d) for 48 weeks. Gynecomastia, breast pain, prostate-specific antigen (PSA), sexual functioning, and serum levels of hormones were assessed. RESULTS: Gynecomastia developed in 73% of patients in the bicalutamide group, 10% of patients in the bicalutamide-tamoxifen group, and 51% of patients in the bicalutamide-anastrozole group (P < .001); breast pain developed in 39%, 6%, and 27% of patients, respectively (P = .006). Baseline PSA level decreased by > or = 50% in 97%, 97%, and 83% of patients in the bicalutamide, bicalutamide-tamoxifen, and bicalutamide-anastrozole groups, respectively (P = .07); and adverse events were reported in 37%, 35%, and 69% of patients, respectively (P = .004). There were no major differences among treatments in sexual functioning parameters from baseline to month 6. Elevated testosterone levels occurred in each group; however, free testosterone levels remained unchanged in the bicalutamide-tamoxifen group because of increased sex hormone-binding globulin levels. CONCLUSION: Anastrozole did not significantly reduce the incidence of bicalutamide-induced gynecomastia and breast pain. In contrast, tamoxifen was effective, without increasing adverse events, at least in the short-term follow-up. These data support the need for a larger study to determine any effect on mortality.

Effects of complete androgen blockade for 12 and 24 weeks on the pathological stage and resection margin status of prostate cancer.

AIMS: To compare the pathological stage and surgical margin status in patients undergoing either immediate radical prostatectomy or 12 and 24 weeks of neoadjuvant hormonal treatment (NHT) in a prospective, randomised study. METHODS: Whole mount sections of 393 radical prostatectomy specimens were evaluated: 128 patients had immediate surgery, 143 were treated for 12 weeks and 122 for 24 weeks with complete androgen blockade. RESULTS: Histopathology revealed organ confined tumours in 40.4% of patients with clinical stage B disease in the immediate surgery group, whereas 12 and 24 weeks of NHT increased the number of organ confined tumours to 54.6% and 64.8%, respectively. Among patients with clinical stage C tumours, pathological staging found organ confined disease in 10.4%, 31.4%, and 61.2% in the immediate surgery, 12 weeks of NHT, and 24 weeks of NHT groups, respectively. Preoperative NHT caused a significant decrease in positive margins both in patients with clinical stage B and C disease. The extent of margin involvement was not influenced by preoperative treatment. CONCLUSIONS: Neoadjuvant androgenic suppression is effective in reducing both the pathological stage and the positive margin rate in patients with stage B and C prostatic cancer undergoing radical surgery. Some beneficial effects are evident in those patients treated for 24 weeks, and it is reasonable to assume that the optimal duration of NHT is longer than three months.

Effect of complete androgen blockade on pathologic stage and resection margin status of prostate cancer: progress pathology report of the Italian PROSIT study.

OBJECTIVES: To compare the pathologic stage and surgical margin status in patients undergoing either immediate radical prostatectomy or surgery preceded by 3 or 6 months of neoadjuvant hormonal treatment (NHT) in a prospective, randomized study. METHODS: Four hundred thirty-one men with prostate cancer were enrolled in the Italian randomized prospective PROSIT study. The whole-mount sectioning technique was used. By May 1999, the reviewing pathologist had evaluated 303 specimens. One hundred seven patients were untreated before radical prostatectomy was performed, and 114 and 82 patients had been treated for 3 and 6 months, respectively, with complete androgen blockade. RESULTS: Pathologic organ-confined disease was found in 63.1% of patients with clinical Stage B disease treated with 6 months of NHT versus 61.0% after 3 months of NHT and 37.5% after immediate surgery. Among patients with clinical Stage C tumors, pathologic staging found organ-confined disease in 62.5%, 32.1%, and 11.1% of patients after 6 months of NHT, 3 months of NHT, and immediate surgery, respectively. Three months of NHT produced a significant increase in negative margins both in patients with clinical Stage B and C disease, but the addition of another 3 months of treatment did not significantly improve this result. A lower degree of benefit was observed in patients with clinical Stage C tumors. CONCLUSIONS: This study shows that complete androgen blockade before surgery is beneficial in men with clinical Stage B disease. The effects are more pronounced after 6 months of NHT than after 3 months.

[Transurethral alprostadil (MUSE) in erectile dysfunction]. / Alprostadil transuretrale (MUSE) nella disfunzione erettile peniena.

The ideal therapy for erectile dysfunction should be easy, non invasive, painless, with a high success and a low side effects rate. Alternative methods of delivery drugs to the erectile body, instead of intracavernosal injection of vasoactive drugs such as prostaglandin, have been evaluated. Vasoactive agents can be administered topically into the urethral mucosa for absorption into the corpus spongiosum and transfer into the corpora cavernosa via small communicating veins. We report data from the literature and our experience with MUSE (Medicated Urethral System for Erection) for the treatment of erectile dysfunction. Penile pain or discomfort is the common adverse effect reported, while no priapism of fibrotic complication is reported. But local discomfort, limited efficacy, and cost are to be considered.

Bicalutamide monotherapy versus flutamide plus goserelin in prostate cancer patients: results of an Italian Prostate Cancer Project study.

PURPOSE: To compare the efficacy of bicalutamide monotherapy to maximal androgen blockade (MAB) in the treatment of advanced prostatic cancer. PATIENTS AND METHODS: Previously untreated patients with histologically proven stage C or D disease (American Urological Association Staging System) were randomly allocated to receive either bicalutamide or MAB. After disease progression, patients treated with bicalutamide were assigned to castration. The primary end point for this trial was overall survival. Secondary end points included response to treatment, disease progression, treatment safety, quality-of-life (QOL), and sexual function. RESULTS: A total of 108 patients received bicalutamide and 112 received MAB. There was no difference in the percentage of patients whose prostate-specific antigen returned to normal levels. At the time of the present analysis (median follow-up time, 38 months; range, 1 to 60 months), 129 patients progressed and 89 died. There was no difference in the duration of either progression-free survival or overall survival. However, a survival trend favored bicalutamide in stage C disease but MAB in stage D disease. Overall and subgroup trends were confirmed by multivariate analysis. Serious adverse events and treatment discontinuations were more common in patients receiving MAB (P =.08 and P =.04, respectively). Fewer patients in the bicalutamide group complained of loss of libido (P =. 01) and of erectile dysfunction (P =.002). Significant trends favored bicalutamide-treated patients also with respect to their QOL, namely relative to social functioning, vitality, emotional well-being, and physical capacity. CONCLUSION: Bicalutamide monotherapy yielded comparable results relative to standard treatment with MAB, induced fewer side effects, and produced a better QOL.

Transurethral electrovaporization of the prostate vs. transurethral resection. Results of a multicentric, randomized clinical study on 150 patients.

AIM OF THE STUDY: To evaluate clinical, urodynamic efficacy and safety of TURP and TVP in patients with symptoms due to obstructive benign prostatic hypertrophy with a prospective multicentric randomized study. MATERIALS AND METHODS: 150 patients with BPH, urodynamically obstructed, were randomized to receive TURP or TVP. At the end of the recruitment phase, 80 patients underwent TURP and 70 patients underwent TVP. Patients were clinically evaluated by the I-PSS score at months 0, 1, 3, 6 and 12. Preoperative evaluation included complete blood routine examination, PSA, transrectal ultrasound and pressure/flow studies. Pressure/flow studies were also performed after 3 months. RESULTS: There was no statistical difference between groups in any of the preoperative parameters. All patients were considered urodynamically obstructed at preoperative pressure studies. As for catheter days and hospitalization days, statistical differences between TVP and TURP were found; catheter days were 2.71 days (SE 0.12) in the TURP group vs. 1.9 (SE 0.24) in the TVP group (p < 0.000). Hospitalization was 4.7 days (SE 0.22) after TURP and 3.9 days (SE 0.24) after TVP (p < 0.000). Mean preoperative I-PSS score was 18.84 and 18.19 in the TVP and TURP groups, respectively. At 3, 6 and 12 months, IPSS was 5.52 and 5.50, 3.77 and 4.94, 3.52 and 4.04 for TURP and TVP, respectively. Mean preoperative peak flow rate (PFR) was 8.78 and 7.26 ml/s for TURP and TVP, respectively; after 3, 6 and 12 months, PFR was 19.21 and 18.8, 20.77 and 20.13, 20.30 and 20.31 ml/s, respectively. After 3 months, 6 patients in the TURP group (7.5%) and 7 patients in the TVP group (10%) were borderline obstructed. 1 patient in the TVP group (1.4%) was still obstructed and underwent TURP. As for complications, 4 patients (5.7%) in the TVP group had stress urinary incontinence after 12 months vs. 1 (1.25%) in the TURP group. DISCUSSION: The present study clearly demonstrates that TVP is as effective as TURP in relieving urinary obstruction due to BPH, it offers some advantages in terms of catheterization and hospital stay, but at the price of a higher incidence of postoperative urine incontinence. Technical improvements might solve this problem in the future, perhaps combining TVP with TURP of the apical tissue.

[Role of BCG in T1G3 bladder transitional cell carcinoma (TCC): our experience]. / Ruolo del BCG nel carcinoma vescicale transizionale (TCC) T1 G3: nostra esperienza.

High grade superficial TCC of the bladder (T1 G3) has an important risk of recurrence and/or progression (40%) after TUR-B and a low survival rate (57% at 3 years, 50% at 10 years). Intravescical treatment with BCG seems to be able to reduce these rates. 64 patients with T1 G3 vescical TCC underwent a "second look" TUR-B. 9/64 patients presented locally advanced tumor (T2-3) or persistent high risk superficial TCC (T1 G3 + Tis) and underwent to early cistectomy. BCG intravescical therapy has been performed in the remaining 55 patients: 10 of them had not been evaluated because local or sistemic toxicity and consequent early interruption of treatment. BCG Pasteur was given weekly at the dose of 75 mg for two cycles of 6 weeks with a rest period of 6 weeks between the two cycles and then monthly for one year and every three months during next two years too. After the first 6 weeks 43/45 patients resulted tumor-free and 2/45 presented persistent Tis: after the second 6 weeks-cycle of BCG, two other patients had evidence of vescical TCC (one T2 G3 and the other T1 G3); all these four patients were submitted to radical cystectomy or radiotherapy. Of the reamining 41 patients, 28 presented had no recurrences, nowadays living and tumor-free; 3 presented local neoplastic progression and dead; relapsed in T1 G2 and are living NED after local chemotherapy. At a mean follow-up of 18 months, the total amount of recurrences is 17/45 (38%), progression rate is 4/45 (8.8%), exitus 5/45 (11%) and living NED are 28/45 (62%). In our opinion local BCG treatment for T1 G3 bladder cancer, after TUR--B, seems to be able to reduce the risk of recurrence and mortality.

[Role of urodynamics in implantation of prostatic stents]. / Ruolo dell'urodinamica nell'impianto degli stents prostatici.

Recent anxieties about the risk of prostate surgery in elderly and unfit patients have generated considerable interest in a number of new permanent prostatic stents. The prostatic Urolume Wallstent was positioned in 34 patients affected by BPH, all with acute or chronic retention of urine, most of whom were unfit for conventional prostatic surgery; the average follow-up is 14 months (range 9-24 months). The stents were inserted with the patients under local or regional anesthesia. 14 patients had prevalent irritative pre-retention symptoms, while in 18 patients obstructive symptoms were dominant; in the remaining 2 patients symptoms were minimal. Cystometry was performed in 29 patients before treatment for evaluation of detrusor activity. Following stent insertion, 31 patients were able to empty satisfactorily, while the remaining 3 patients presented chronic retention because of detrusor failure, evidenced before treatment. Most patients experienced frequency and urgency for several months (90% of 14 patients with pre-treatment irritative symptoms; 25% of the other 20 patients). No incrustation occurred, no serious urosepsis was registered. In 3 patients we need to put in a second stent. In the first weeks, 4 stents were removed for dislocation and then replaced endoscopically without difficulty or damage to the urethra. After 6 months, other 5 stents were definitively removed because of persistent unbearable irritative symptoms with poor quality of life (all these patients had severe pre-operative detrusor overactivity).(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian continuous chemotherapy of renal cell carcinoma with an implantable, programmable infusion pump.

The authors treated 42 metastatic renal cell carcinoma (RCC) patients who had received no previous chemotherapy or radiation therapy with circadian venous continuous infusion of 5-fluoro-2-deoxyuridine (FUDR). The drug was delivered by Medtronic Synchromed implantable pump (Medtronic, Inc., Minneapolis, MN) in 14-day cycles alternating with 14-day intervals of heparinized physiologic saline infusion. In the course of 24 months 444 cycles of therapy have been given for a total of 12449 days of pump function. Of the patients observed for at least 3 months (range, 3 to 23 months; median, 7 months) three showed complete response (7%; 95% confidence interval, 0% to 15%), three partial response (7%; confidence interval, 0% to 15%), 18 stable disease, and 18 showed progression. Eighteen patients, all with advanced disease at the time of implantation, were living 6 months after treatment started. Circadian continuous central venous infusion of FUDR is minimally toxic. The FUDR can be delivered safely and conveniently in this way for long spans. This therapy is as active as any currently available treatment, is administered in an entirely outpatient setting, and is associated with a normal quality of life.

Cortical and medullary kidney tissue levels of cefonicid in human beings.

Cefonicid concentration has been determined microbiologically in cortical and medullary tissue in 30 patient undergoing surgery because of neoplastic disease localized within the kidney. Each subject received 1 g of cefonicid intramuscularly in a single administration. The patients were divided into six groups, from which samples of blood and tissue were collected 2, 4, 6, 8, 12, 24 h respectively after treatment with the drug. The mean peak serum levels appeared at the second hour (74.96 +/- 8.14 mcg/ml) and the decay shows a monoexponential behaviour, reaching a minimum value of 5.4 +/- 2.33 mcg/ml at the 24th hour. In the cortical tissue of the kidney the peak levels appeared at the fourth hour (26.22 +/- 8.87 mcg/g), while at the 24th hour levels were about 3.08 +/- 0.81 mcg/g. A very similar behaviour could also be observed in the medullary tissue of the kidney with peak levels at the fourth hour (25.82 +/- 10.06 mcg/g) and levels of 3.48 +/- 0.85 mcg/g at the 24th hour. A delay in the decay of tissue levels in comparison with the decay of blood levels could be observed from the eighth hour.

Progestogens in renal cell carcinoma. A retrospective study.

A retrospective study of 88 cases of renal cell carcinoma is presented with emphasis on the follow-up and progestogens administration. Between the statistically homogeneous groups of patients treated with progesterone capronate and with other therapeutic regimens, no statistical difference in actuarial survival rate could be detected.