To determine whether tamoxifen or anastrozole prevents gynecomastia and breast pain caused by bicalutamide (150 mg) without compromising efficacy, safety, or sexual functioning.
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.
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.
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.
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.
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.
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.
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.
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.
To evaluate the activity and safety of intravesical instillations of 80 mg epirubicin in a selected patient population with T1G2 primary and multiple superficial bladder tumors. To assess the ...completeness of the transurethral resection (TUR) at 4 weeks (second look) and to compare the histology of local and review pathology.
One hundred and sixty-nine patients have been histologically assessed both locally and extramurally for T1G2 superficial bladder tumors. Epirubicin (80 mg/instillation) started within 20 days after TUR was administered weekly during the first month and then monthly for another 11 months. Assessments for relapse were carried out according to the standard methods.
Histological consistency for T1G2 between local and extramural assessments was found in 85.2% of cases. At the median follow-up time of 38 months, the overall relapse rate was 43.3%. Treatment was very well tolerated: no systemic adverse events were reported and local adverse events were confined to chemical cystitis which in 3% required treatment discontinuation.
Epirubicin (80 mg/instillation) appeared effective in the prophylaxis of relapse in primary and multiple T1G2 superficial bladder tumors. A second TUR at 3-4 weeks is necessary in T1 tumors. Excellent concordance between local and review pathology was found.
To compare the efficacy of bicalutamide monotherapy to maximal androgen blockade (MAB) in the treatment of advanced prostatic cancer.
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.
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.
Bicalutamide monotherapy yielded comparable results relative to standard treatment with MAB, induced fewer side effects, and produced a better QOL.
Interferons have shown a definite activity in the intravesical treatment of residual papillary bladder cancer or carcinoma in situ (CIS). The purpose of the present study was to investigate the ...efficacy of interferon alfa-2b (IFN) as prophylactic treatment of superficial bladder cancer.
Two hundred eighty-seven patients with primary pTa G2, pT1 G1 to G2 superficial bladder cancer, following complete transurethral resection (TUR), were randomly allocated to receive intravesical treatment, either with IFN (50 x 10(6) IU) or mitomycin (MIT-C; 40 mg). Drugs were instilled on a weekly basis for a total of 8 weeks.
MIT-C was superior to IFN treatment with respect to time to recurrence, relative recurrence rate, recurrence rate per 100 patients per month, and recurrence tumor rate per 100 patients per month. This difference was particularly evident in patients with pTa G2 tumors. After multivariate analysis, the number of primary tumors and tumor grade were the best predictors of recurrence, while allocated treatment had only a moderate effect. Intravesical treatment was well tolerated in both arms. However, more local toxicity was experienced by patients treated with MIT-C. On the other hand, fever occurred significantly more frequently in patients treated with IFN.
IFN was less effective, although locally better tolerated, than MIT-C as prophylactic treatment of primary superficial bladder cancer.
Objectives:
To compare the efficacy of bicalutamide monotherapy to maximal androgen blockade in advanced prostatic cancer.
Patients and Methods:
Previously untreated patients with histologically ...proven stage C or D (American Urological Association Staging System) disease were randomly allocated to either bicalutamide (B) or goserelin plus flutamide (G+F). After disease progression, patients treated with B were assigned to castration. The primary endpoint for this trial was overall survival. Prostate cancer-specific survival and progression were included among secondary endpoints.
Results:
In total 108 patients received B and 112 received G+F. At a median follow-up time of 54 months (range 1–89), 151 patients progressed and 113 died. There was no significant difference in the duration of either progression-free or overall survival. Hazards of progression, death and cancer-specific death, corrected by disease stage, tumor grade and baseline PSA level, showed that patients initially assigned to B had a higher risk of progression but a comparable risk of death and cancer-specific death with the exception of patients with G3 tumors who had an increased risk of death).
Conclusions:
In patients with well or moderately well differentiated tumors, B monotherapy followed by castration may offer the same survival chance as maximal androgen deprivation. In those patients it thus represents a reasonable choice that can avoid the side effects of androgen deprivation for considerable periods of time.
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.
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.
To determine whether tamoxifen or anastrozole prevents gynecomastia and breast pain caused by bicalutamide (150 mg) without compromising efficacy, safety, or sexual functioning.
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.
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 ≥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.
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.
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