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M Soloway

Publications and source records attributed to M Soloway.

At least 19 recordsLinked to original sources
PubMed2000

The use of liver transplant techniques to aid in the surgical management of urological tumors.

PURPOSE: Inferior vena cava tumor thrombus complicates radical nephrectomy. Various approaches have been used to deal with this problem, including venovenous and cardiopulmonary bypass. Applying organ transplant techniques enhances the exposure of urological tumors and may avoid bypass. MATERIALS AND METHODS: A total of 26 patients underwent surgery by techniques developed to facilitate orthotopic liver transplantation. Of the patients 15 with renal cell carcinoma and an intracaval tumor thrombus underwent piggyback style mobilization of the liver off of the retrohepatic inferior vena cava to allow enhanced access and vascular control, while 11 underwent conventional mobilization of the liver and retrohepatic inferior vena cava en bloc to allow enhanced access to various renal, adrenal and retroperitoneal tumors. RESULTS: In the 11 patients surgery was successful with a median blood loss of 200 ml. Postoperative ileus in 1 case was the only complication. We resected 5 infrahepatic thrombi without complications and with a median blood loss of 500 ml. In 7 patients with a retrohepatic inferior vena caval thrombus median blood loss was 1,500 ml., including 1 who died postoperatively, presumably due to a massive pulmonary embolus. Caval atrial tumor thrombus in 3 cases was successfully removed via a completely abdominal approach and sternotomy in 2. Cardiopulmonary bypass with hypothermic circulatory arrest was required in 1 of these cases. CONCLUSIONS: Liver mobilization was helpful for managing difficult urological tumors. Patients with a retrohepatic or even suprahepatic inferior vena caval thrombus may be treated without sternotomy or thoracotomy and cardiopulmonary bypass.

Adolescent↗
PubMed1999

Neoadjuvant Hormonal Therapy Prior to Radical Prostatectomy.

The US T(2b) study of 3 months of neoadjuvant hormonal therapy (NHT) showed a reduction in the likelihood of positive margins from 48% (control group) to 18% in the treated patients. Follow-up at 42 months shows that the cumulative relapse rate (prostate specific antigen) for 129 patients having NHT was not statistically different from that of the 126 control patients. Because the T(2b) study has been criticized for lacking central pathology review, we present a review of a series involving only one surgeon (MS) and one pathologist (FC) of NHT plus prostatectomy (109 patients) v prostatectomy alone (145 patients) with 24 months' follow-up. Positive margins were decreased from 38% in the untreated to 28% in the treated group, the only statistically significant difference in the results. Biochemical recurrence (PSA >0.2 ng/mL) was higher in the treated group, reflecting selection of more aggressive tumors for NHT, but the difference was not statistically significantly. The incidence of extracapsular extension, seminal vesicle invasion, and lymph node metastasis was similar in the two groups. The largest nonrandomized experience with NHT shows a decrease in the incidence of positive surgical margins when used in high-risk patients with clinically localized carcinoma of the prostate. However, it does not have an impact on disease-free survival at a mean 24-month follow-up.

Journal Article↗
PubMed1998

Casodex 10-200 mg daily, used as monotherapy for the treatment of patients with advanced prostate cancer. An overview of the efficacy, tolerability and pharmacokinetics from three phase II dose-ranging studies. Casodex Study Group.

OBJECTIVES: To evaluate the efficacy, tolerability, endocrinological effects and the pharmacokinetics of Casodex, when given as monotherapy during daily dosing of 10-200 mg to patients with advanced prostate cancer. METHODS: A total of 390 patients with advanced prostate cancer were treated for a minimum of 12 weeks with a daily monotherapy dose of Casodex. The doses ranged from 10 to 200 mg. Objective assessments of efficacy included: review of measurable metastases, prostate dimension, prostatic acid phosphatase and prostate-specific antigen (PSA) levels. Subjective assessments of efficacy included review of urological symptoms, performance status, bone scan and analgesic requirement. Pharmacokinetic samples were taken at various time points up to 3 months, and assayed using an achiral HPLC method. RESULTS: Clear objective responses were observed, particularly at doses of 50 mg and above. Specifically, the median percentage decrease in PSA at 50 mg was 90.0%, and at 100 and 200 mg it was 93.4 and 94.8%, respectively. Up to 53% of symptomatic patients demonstrated a subjective response at 3 months. Casodex was well tolerated at all doses with no effect on haematological or cardiovascular parameters and no effect on renal function. The expected pharmacological effects of potent antiandrogen therapy, such as breast tenderness (58%), gynaecomastia (48%), and hot flushes (17%), were reported, but these incidences reflected the direct eliciting of these events. The intrinsic efficacy of Casodex was demonstrated despite increases of 60% in testosterone levels. However, this increase reached a plateau after 4-12 weeks of therapy, but the majority of values remained within the normal range. Casodex has a half-life of approximately 1 week, enabling once-daily dosing with no effect of age or renal impairment on its pharmacokinetics. CONCLUSION: Casodex has a favourable side effect profile compared with the known safety profiles of other antiandrogens and has demonstrated intrinsic efficacy. Casodex warrants further investigation as a monotherapy for the management of advanced prostate cancer.

Acid Phosphatase↗
PubMed1997

PSA levels and the rate of positive surgical margins in radical prostatectomy specimens preceded by androgen blockade in clinical B2 (T2bNxMo) prostate cancer. The Lupron Depot Neoadjuvant Study Group.

OBJECTIVES: Neoadjuvant hormonal therapy reduces positive margins in patients undergoing radical prostatectomy. All patients experience a decrease in serum prostate specific antigen (PSA), but not always to a level that is nondetectable. The results of several prospective, randomized trials indicate that the incidence of positive margins decreases with the use of androgen deprivation prior to radical prostatectomy. It has been suggested that a greater decline in PSA levels would result in fewer positive margins. In a recent US trial of patients with T2bNxMO prostate cancer, we reported that 18% of patients randomized to receive 3 months of leuprolide acetate and flutamide had positive margins, compared to 48% of those who had radical prostatectomy alone (P < 0.001). We correlated the PSA levels prior to and following androgen deprivation and the presence of a positive margin following radical prostatectomy (RP). METHODS: One hundred and thirty-seven of 149 patients randomized to receive presurgery androgen deprivation (AD) underwent radical prostatectomy. Of these, 135 had a PSA level obtained both prior to androgen deprivation and prior to surgery. We analyzed the percent positive margins in patients whose PSA values became undetectable and in those whose values remained above 0.1 ng/mL despite androgen deprivation. RESULTS: Eight of 43 patients (19%) with a nadir PSA < or = 0.1 ng/mL had a positive surgical margin and 16/92 (17%) with a nadir PSA > 0.1 ng/mL had tumor at the margin. There were no statistical differences in these two groups (P = 1.0 by Fisher's Exact Test [two-tailed], and the Pearson correlation was -0.015). CONCLUSIONS: There was no correlation between an undetectable PSA and a PSA > 0.1 ng/mL and the presence of tumor at the margin when 3 months of AD was given prior to RP. It is possible that longer periods of AD prior to RP will reduce PSA to an undetectable level in a higher percent of patients. However, these data suggest that an undetectable level will not result in less positive margins.

Aged↗
PubMed1997

Assessment of endpoints for clinical trials for localized prostate cancer.

OBJECTIVES: The AUA Practice Guidelines Panel convened to address the issue of appropriate endpoints for assessment of treatment modalities for localized carcinoma of the prostate. METHODS: A review of the literature and the design of existing clinical trials produced a consensus, which was presented to and critiqued by the members of the general conference. RESULTS: The pitfalls associated with identification of local failure endpoints were discussed, and the more accurate endpoints of freedom from metastatic progression and overall survival were recognized. The strict definition that must be fulfilled for intermediate endpoints to become surrogates for metastasis free and/or survival endpoints was stressed. For more efficient and rapid conduct of future clinical trials, the urgent need to validate such surrogate endpoints by evaluation in randomized control trials is obvious. PSA, while an indicator of disease activity and a critical marker for estimating disease progression or regression in response to therapy, is not a surrogate for metastasis free or overall survival. CONCLUSION: Until surrogate endpoints are validated, the committee has evaluated the endpoints in current use, reviewed their limitations, and stressed the importance of quality-of-life assessment together with the traditional endpoint assessment.

Clinical Trials as Topic↗
PubMed1996

Maximal androgen blockade for patients with metastatic prostate cancer: outcome of a controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy. Casodex Combination Study Group.

OBJECTIVES: To review the outcome of therapy with maximal androgen blockade and compare the efficacy and safety of bicalutamide and flutamide, each used in combination with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy, in patients with untreated metastatic (Stage D2) prostate cancer. METHODS: Randomized, double-blind (for antiandrogen therapy), multicenter study with a 2 x 2 factorial design. A total of 813 patients were allocated 1:1 to bicalutamide (50 mg once daily) or flutamide (250 mg three times daily), plus 2:1 to goserelin acetate (3.6 mg every 28 days) or leuprolide acetate (7.5 mg every 28 days). RESULTS: At the time of analysis (median follow-up, 49 weeks), bicalutamide plus LHRH-A was associated with a statistically significant improvement in time-to-treatment failure, the primary endpoint, when compared with flutamide plus LHRH-A. The results with longer follow-up (median, 95 weeks) support previous findings of an improved time-to-treatment failure with bicalutamide plus LHRH-A; however, the difference between groups was not statistically significant. A treatment failure endpoint was reached by 68% of patients in the bicalutamide plus LHRH-A group, compared with 72% of patients in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.87 (95% confidence interval [CI], 0.74-1.03; P = 0.10). The upper one-sided 95% confidence limit for survival was 1.00, meeting the definition for equivalence (< 1.25). With longer follow-up, overall mortality was 34%, with equivalent survival between groups: 32% of patients in the bicalutamide plus LHRH-A group died, compared with 35% in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.88 (95% CI, 0.69-1.11; P = 0.29). The upper one-sided 95% confidence limit for survival was 1.07, meeting the definition for equivalence (< 1.25). Diarrhea occurred in 24% of patients in the flutamide plus LHRH-A group compared with 10% of patients in the bicalutamide plus LHRH-A group (P < 0.001). CONCLUSIONS: In patients with metastatic prostate cancer, bicalutamide plus LHRH-A is effective and well tolerated. Because of its efficacy and tolerability profile, together with its convenient once-daily dosing formulation, bicalutamide represents a prime candidate for antiandrogen of first choice in combination with LHRH-A therapy in the treatment of men with metastatic prostate cancer.

Adult↗
PubMed1996

Incidental prostatic adenocarcinoma in patients undergoing radical cystoprostatectomy for bladder cancer.

To determine if patients with bladder cancer have a higher incidence of unsuspected prostate cancer, 40 cases were studied. All except one case had no evidence of prostate cancer on preoperative clinical assessment. Detailed pathological evaluation of cystoprostatectomy specimens with sections at 2- to 3-mm intervals was done. Adenocarcinoma of the prostate was identified in 18 of 40 patients (45%). Multifocal prostatic intraepithelial neoplasia (PIN) was present in 19 cases (47.5%); 4 (10%) without an associated prostate cancer and 15 (37.5%) in conjunction with adenocarcinoma of the prostate. Twelve cases of unsuspected prostate cancer were stage pT1a, 4 were pT1b, and 2 were pT3. No patients exhibited nodal or distance metastases by the prostate cancer. At a mean follow-up of 15.2 months (range 3-34 months), 37 of the 40 patients are alive. Among prostate cancer patients, no clinical or biochemical evidence of disease recurrence or prostate cancer related mortality has been observed. Our findings support the previously reported high incidence rate of prostate cancer in patients undergoing cystoprostatectomy for bladder cancer. This, though, may not be higher than the observed incidence in an age-matched general population. We recommend DRE and PSA as part of the bladder cancer workup in males, and complete removal of the prostate at cystoprostatectomy to prevent the dilemma of residual prostate cancer.

Adenocarcinoma↗
PubMed1995

Treatment with finasteride following radical prostatectomy for prostate cancer.

OBJECTIVES: The objective of this study was to evaluate the effect of finasteride (10 mg/d) or placebo on serum prostate-specific antigen (PSA) and recurrence rates in men with detectable PSA levels after radical prostatectomy. METHODS: A total of 120 men, 48 to 89 years old, previously treated with radical prostatectomy for prostate cancer within the past 10 years, with serum PSA levels between 0.6 and 10.0 ng/mL, with no evidence of skeletal metastasis on bone scan, and with no previous androgen deprivation therapy, were treated with 10 mg finasteride or placebo in a double-blind fashion for 12 months. After the first year, all patients were treated with finasteride for an additional 12 months. Primary endpoints were serum PSA levels and recurrence rates defined as positive bone scan or positive biopsy. RESULTS: Patients treated with finasteride had a delayed increase in serum PSA compared with placebo of approximately 9 months in the first year and 14 months by the end of the second year. Patients with baseline PSA levels less then 1.0 ng/mL had no significant increase in serum PSA during the 2 years of treatment. Fewer recurrences were observed in the finasteride group, but these differences were not statistically significant. Finasteride was well tolerated, and side effects were balanced between treatment groups. CONCLUSIONS: The results of this study indicate that treatment with finasteride delays but does not prevent the rise in serum PSA observed in untreated patients with detectable PSA levels after radical prostatectomy. The reduction in local and distant recurrences in the finasteride group suggests that the effect on PSA reflects a direct effect on tumor growth without affecting the initial response to subsequent hormonal therapy. These data require confirmation by studies that are longer and larger, focused on demonstrating significant differences in progression rates and survival before the use of finasteride can be considered as an option for men with detectable PSA levels after radical prostatectomy.

Aged↗
PubMed1995

A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Casodex Combination Study Group.

OBJECTIVES: To compare the efficacy and safety of bicalutamide and flutamide, each used in combination with luteinizing hormone-releasing analogue (LHRH-A) therapy, in patients with untreated metastatic (Stage D2) prostate cancer. METHODS: Randomized, double-blind (for antiandrogen therapy), multicenter study with a 2 x 2 factorial design. Eight hundred thirteen patients were allocated 1:1 to bicalutamide (50 mg once daily) and flutamide (250 mg three times daily) and 2:1 to goserelin acetate (3.6 mg every 28 days) and leuprolide acetate (7.5 mg every 28 days). RESULTS: With a median duration of follow-up of 49 weeks, time to treatment failure, the primary endpoint, was significantly (P = 0.005) better for the bicalutamide plus LHRH-A group than for the flutamide plus LHRH-A group. Patients in the flutamide plus LHRH-A group were 34% more likely to fail treatment over the given time period, as indicated by the hazard ratio of 0.749 (95% confidence interval, 0.61 to 0.92) for bicalutamide plus LHRH-A to flutamide plus LHRH-A. Results for secondary endpoints (survival, quality of life, and subjective response) were similar between groups. Diarrhea occurred in 24% of patients in the flutamide plus LHRH-A group, compared with 10% of patients in the bicalutamide plus LHRH-A group (P < 0.001). CONCLUSIONS: In patients with metastatic prostate cancer, bicalutamide plus LHRH-A is well tolerated and provides superior efficacy to flutamide plus LHRH-A with respect to time to treatment failure. Assessment of the effects of these regimens on longer term survival requires additional time for follow-up.

Adenocarcinoma↗
PubMed1992

Distant disease.

Explore the source record for details and available documents.

Androgen Antagonists↗
PubMed1992

A randomized, placebo-controlled multicenter study of the efficacy and safety of terazosin in the treatment of benign prostatic hyperplasia.

The clinical manifestations of benign prostatic hyperplasia (BPH) are related primarily to bladder outlet obstruction resulting from enlargement of the prostate gland. Transurethral prostatectomy is the most common treatment currently offered for BPH in the United States. The primary objective of the present randomized placebo controlled multicenter study was to determine the efficacy and safety of terazosin, a selective long-acting alpha 1-blocker, for the treatment of symptomatic BPH. A total of 285 men with symptomatic BPH was randomly assigned in equal proportions to receive placebo, or 2, 5 or 10 mg. terazosin administered once daily. Of the patients 237 completed the 4-week single-blind placebo lead-in and 12-week double-blind treatment periods. The primary outcome parameters were changes in peak and mean urinary flow rates, and changes in the Boyarsky symptom scores. All terazosin treatment groups exhibited significantly greater decreases in total Boyarsky symptom score than the placebo group. The 10 mg. terazosin group exhibited significantly greater increases in peak and mean urinary flow rates than the placebo group. The improvements in symptom scores and urinary flow rates did not reach a plateau within the dose range evaluated, suggesting that further efficacy may be achieved with doses of terazosin exceeding 10 mg. This study unequivocally demonstrates the safety and efficacy of terazosin for the treatment of BPH. Selective alpha 1-blockade is likely to gain widespread acceptance for the treatment of BPH due to its safety and efficacy.

Adrenergic alpha-Antagonists↗
PubMed1992

The prognostic value of the pathological response to combination chemotherapy before cystectomy in patients with invasive bladder cancer. European Organization for Research on Treatment of Cancer--Genitourinary Group.

The prognostic value of the pathological response to combination chemotherapy of deeply invasive transitional cell cancer of the bladder was retrospectively assessed in 147 patients. Data were collected from 8 different centers. Patients were eligible if they had received intravenous combination chemotherapy followed by partial, total or radical cystectomy, and if they had a minimum followup of 2 years after the start of chemotherapy. Of the patients 90% received methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) or cisplatin plus methotrexate for a median of 3 courses (range 1 to 6). Of the 83 patients who were alive at analysis actuarial median followup was 30.5 months (range 13.2 to 85.6 months). A major pathological response (stage P0, Pis, Pa or P1) was achieved in 41.5% of the patients. Patients with a major pathological response (p stage less than 2) had a 5-year survival of 75% in contrast to 20% for the remaining nonresponding patients (p stage 2 or more). The survival of patients with a major pathological response was independent of whether the response was induced by 2 or more courses of chemotherapy, or whether it was induced by M-VAC in comparison with cisplatin plus methotrexate. Preoperative clinical assessments can identify nonresponding patients correctly and in these cases alternative treatment programs are required, since 80% will die of the disease. Moreover, if neoadjuvant chemotherapy is proved to increase survival, the data emphasize the importance of the response rate of the primary tumor and the need to investigate the optimal number of courses to induce the best response, preferably in the individual patient.

Actuarial Analysis↗
PubMed1991

Independent prognostic factors in patients with metastatic (stage D2) prostate cancer. The Zoladex Study Group.

The independent prognostic factors affecting survival were assessed in 240 men undergoing treatment for metastatic prostate cancer as part of a randomized clinical trial comparing the gonadotropin releasing hormone analogue Zoladex (goserelin acetate implant) with castration. In a multivariate analysis, the most highly significant predictors were the presence or absence of bone pain, serum testosterone levels, serum alkaline phosphatase levels, and performance status. Patients with all four factors favorable for survival had a 2-year survival rate of 84% as compared with only 8% for patients with none of the four factors favorable for survival. No other factors were significant. A separate analysis of serum testosterone levels revealed that the higher the pretreatment serum testosterone level, the greater the survival rate. Compared with patients with serum testosterone levels less than 6.9 nmol/L, significant differences in survival were observed for patients with serum testosterone levels of 10.4 to 13.9, 13.9 to 17.3, and over 17.3 nmol/L. These results have important implications for the design and analysis of future clinical trials of hormone therapy and for counseling patients regarding the short-term prognosis of their disease.

Alkaline Phosphatase↗
PubMed1990

Clinical study of leuprolide depot formulation in the treatment of advanced prostate cancer. The Leuprolide Study Group.

In a phase III, open, multicenter study we evaluated the safety and efficacy of the depot formulation of leuprolide (7.5 mg. injected intramuscularly every 4 weeks) in patients with stage D2 prostate cancer who had not previously received systemic treatment. Serum testosterone, luteinizing hormone and plasma leuprolide levels were monitored during the 24-week study period. Median interval to onset of castrate testosterone levels was 21 days and mean testosterone levels decreased to within the castrate range by week 3 of treatment. After onset of castrate levels there were no escapes (defined as 2 consecutive values of greater than 50 ng./dl.) of testosterone levels during the 24 weeks. Suppression of testosterone did not differ significantly from that observed in patients receiving the daily subcutaneous injection of leuprolide acetate in the first 24 weeks of another study. Objective response (no progression) to treatment occurred in 81% of 53 evaluable patients and adverse (related and unrelated) events were reported in 45 of the 56 patients. The response rate and incidence of adverse events in this study did not differ significantly from those occurring with the daily formulation. We conclude that the depot formulation of leuprolide is safe and effective in the treatment of advanced prostatic cancer, and that the safety and efficacy of this formulation do not differ significantly from those of the daily subcutaneous formulation.

Aged↗
PubMed1990

'Acute on chronic' effect of depot leuprolide in patients with stage D2 cancer of prostate.

During a phase III open study of depot leuprolide for stage D2 cancer of the prostate, we studied the effect of depot leuprolide on chronic leuprolide users. To determine whether there was a transient elevation of testosterone or luteinizing hormone (LH) 4-24 h and 3-5 days following the monthly injections, we monitored the changes of testosterone and LH before injection and 24 h post-injection in 10 patients who have been under depot leuprolide Rx for 24-36 weeks, and in 35 patients before injection and 3-5 days post-injection who have received depot leuprolide for 8-24 weeks prior to monitoring. Comparison of the data between pre-injection within 24 h and 3-5 days post-injection showed no significant changes of testosterone and LH values between these levels for either testosterone (P = 0.31) or LH (P = 0.45). We therefore conclude that there was no 'acute on chronic' effect of depot formulation in chronic users of depot leuprolide.

Clinical Trials as Topic↗
PubMed1989

Treatment of early prostate cancer.

For the treatment of locally advanced prostate cancer, agents that induce androgen deprivation might be given several months prior to radical prostatectomy with the hope of reducing the size and extent of tumour prior to surgery.

Humans↗
PubMed1988

Intravesical thiotepa versus mitomycin C in patients with Ta, T1 and TIS transitional cell carcinoma of the bladder: a phase III prospective randomized study.

A prospective randomized clinical trial was conducted by the National Bladder Cancer Group to compare thiotepa and mitomycin C in ablating residual Ta, T1 and TIS transitional cell carcinoma of the bladder. Eight weekly instillations were given followed by cystoscopy 4 weeks after the treatment was stopped. The over-all complete response rate based on cystoscopy and either biopsy or cytology was 26 per cent for thiotepa versus 39 per cent for mitomycin C (p equals 0.08). The greatest efficacy was seen in the Ta group with mitomycin C demonstrating superiority over thiotepa. Patients with negative cystoscopy and biopsy but who had positive cytology were considered to be partial responders. When partial and complete responders were combined the over-all response rate was 53 per cent for thiotepa and 63 per cent for mitomycin C (p equals 0.23). Patients with TIS appeared to respond equally to thiotepa and mitomycin C. Toxicity included urinary frequency in 22 of the 73 patients in the thiotepa arm and 31 of the 76 patients receiving mitomycin C. A rash was observed in 2 of the thiotepa group versus 14 of the mitomycin C group. Bone marrow depression occurred in 15 patients receiving thiotepa and in 12 receiving mitomycin C.

Administration, Intravesical↗