Search PubMed⌕ Search

Biomedical subjects

R Sharifi

Publications and source records attributed to R Sharifi.

At least 19 recordsLinked to original sources
PubMed2000

Evaluation of an implant that delivers leuprolide for 1 year for the palliative treatment of prostate cancer.

OBJECTIVES: To evaluate the Viadur implant, which delivers leuprolide acetate for the palliative treatment of advanced prostate cancer. METHODS: Inserted subcutaneously, the 4 x 45-mm implant uses osmotic pressure to deliver leuprolide continuously at a controlled rate for 1 year. This 19-center open-label study enrolled patients with prostate cancer who had had no prior therapy or showed biochemical evidence of treatment failure after prostatectomy or radiotherapy. Each patient received one implant. After 1 year, that implant was removed, another was inserted, and patients were followed up for 2 additional months. The primary efficacy measure was suppression of testosterone to less than the castrate threshold (50 ng/dL). RESULTS: Eighty patients were enrolled. The implant effectively suppressed testosterone in 79 patients (99%) within 2 to 4 weeks and maintained that suppression through the study period. In 1 patient, the testosterone was suppressed to less than 100 ng/dL within 4 weeks but was not less than 50 ng/dL until week 24. Prostate-specific antigen levels normalized (4 ng/mL or less) or a clinically significant decrease occurred in all patients. Leuprolide was rapidly absorbed, resulting in mean serum concentrations of 16.8 ng/mL 4 hours after implant insertion and 2.4 ng/mL at 24 hours; steady mean serum leuprolide concentrations were then maintained throughout the year, at approximately 0.9 ng/mL. Investigators were satisfied with the insertion and removal procedures. All patients reported satisfaction after 1 year of treatment. The safety profile of the implant was consistent with androgen ablation therapy. Most adverse events were mild, and the most common event was hot flashes. CONCLUSIONS: The leuprolide implant effectively suppressed testosterone concentrations to less than the castrate threshold and maintained that suppression throughout the study period.

Aged↗
PubMed1999

Exploratory analysis on the effect of race on clinical outcome in patients with advanced prostate cancer receiving bicalutamide or flutamide, each in combination with LHRH analogues. The Casodex Combination Study Group.

BACKGROUND: Black race has been associated with a significantly increased risk of prostate cancer mortality. This exploratory analysis investigated the effect of race on the clinical outcome of combined androgen blockade (CAB). METHODS: Data for analysis were obtained from a double-blind, randomized, multicenter trial comparing CAB in the form of bicalutamide (50 mg once daily) or flutamide (250 mg three times daily) plus luteinizing hormone-releasing hormone analogs (LHRHa; goserelin acetate 3.6 mg, or leuprolide acetate 7.5 mg) in 813 patients with stage D(2) prostate cancer (median follow-up, 160 weeks). Patients were analyzed according to race (African American [AA], white, or other). The primary clinical events were disease progression and survival. RESULTS: Four hundred and four patients received bicalutamide/LHRHa and 409 received flutamide/LHRHa. Although treatment with bicalutamide/LHRHa resulted in slightly longer time to progression and survival time in white and AA males than treatment with flutamide/LHRHa, the differences between the treatment groups were not statistically significant. CONCLUSIONS: No marked effect of race on clinical outcome was observed regardless of antiandrogen, suggesting that similar treatment benefits are to be expected in either race.

Adenocarcinoma↗
PubMed1999

A multi-attribute model of prostate cancer patient's preferences for health states.

Multi-attribute utility theory (MAUT) provides a way to model decisions involving trade-offs among different aspects or goals of a problem. We used MAUT to model prostate cancer patients' preferences for their own health state and we compared this model to patients' global judgments of health state utility. 57 patients with prostate cancer (mean age = 70) at two Chicago Veterans Administration health clinics were asked to evaluate health states described in terms of five health attributes affected by prostate cancer: pain, mood, sexual function, bladder and bowel function, and fatigue and energy. Each attribute had three levels that were used to form three clinically realistic health state descriptions (A = high, B = moderate, C = low). A fourth personalized health description (P) matched the patient's current health. We first measured patients' preferences using time trade-off (TTO) judgments for the three health states (A, B, and C) and for their own current health state (P). The TTO for the patient's own health state (P) was standardized by comparing it to TTO judgments for states A and C. We next constructed a multi-attribute model using the relative importance of the five attributes. The MAU scores were moderately correlated with the TTO preference judgments for the personalized state (Pearson r = 0.38, N = 57, p < 0.01). Thus, patients' preference judgments are moderately consistent and systematic. MAUT appears to be a potentially feasible method for evaluating preferences of prostate cancer patients and may prove helpful in assisting with patient decision making.

Aged↗
PubMed1999

Quality of life in low-income patients with metastatic prostate cancer: divergent and convergent validity of three instruments.

Few studies have evaluated Quality Of Life (QOL) among low-income patients with cancer. Information is needed about the feasibility and psychometric characteristics of QOL instruments in these populations. The purpose of this study was to examine the convergent and discriminant relationships between scales of three QOL instruments: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC), Functional Assessment of Cancer Therapy--General (FACT), and Quality of Life Index (QLI). Participants included 110 men with metastatic prostate cancer of whom 94% were low income and 62% were African-American. Interviewers administered the questionnaires. Cronbach alpha internal consistency reliabilities were 0.57 to 0.90 for the EORTC, 0.65 to 0.86 for the FACT, and 0.63 for the QLI. Convergent validity was supported for the EORTC and FACT scales measuring emotional, physical, and role/functional dimensions (r = 0.54 to 0.72), but not on scales measuring social function (r = 0.12). Divergent validity was supported between dissimilar scales (r = 0.14 to 0.38). Analysis with receiver operating characteristics curves provided empirical support for the EORTC and FACT as multidimensional measures. These findings suggest that, even in busy clinical settings with low literacy patients, interviewer-administered EORTC and FACT QOL instruments can provide valid and reliable information.

Aged↗
PubMed1998

Leuprolide acetate (30-mg depot every four months) in the treatment of advanced prostate cancer.

OBJECTIVES: An unblinded, multicenter study to evaluate the efficacy and safety of a long-acting depot formulation of leuprolide (30 mg injected intramuscularly every 16 weeks) was carried out in 49 patients with Stage D2 prostate cancer. METHODS: Clinical evaluations were performed every 16 weeks, and serum testosterone levels were monitored biweekly or weekly for 32 weeks. RESULTS: The mean serum testosterone level for the 45 evaluable patients fell to the castrate range (50 ng/dL or less) by week 3 after the initial depot injection and remained at that level throughout the initial 32-week treatment period. The median time to the onset of castrate levels was 22 days (range 9 to 43). Onset of castrate levels of testosterone was achieved within 4 weeks of the initial depot injection in 96% of patients. One patient (2%) experienced a transient "escape" (testosterone levels greater than 50 ng/dL on two consecutive determinations). Delay of an injection by up to 3 weeks did not have an effect on testosterone suppression. Objective tumor response (no progression) occurred in 90% of patients at week 16 and in 80% at week 32. Prostate-specific antigen and prostatic acid phosphatase decreased by 50% or more at week 32 in 97% and 76% of patients, respectively. Assessment of local disease status and overall performance status showed improvement or stability in most patients. The most common adverse events were hot flashes (45%), back pain (16%), and arthralgia (14%). CONCLUSIONS: The 30-mg depot formulation of leuprolide, which acts in a manner similar to the 7.5- and 22.5-mg depot formulations (given monthly and every 3 months, respectively) is effective in lowering serum testosterone to castrate levels in all patients and demonstrates a favorable response in 80% of the patients with advanced prostate cancer for the 32-week observation period. The drug was well tolerated in all patients.

Acid Phosphatase↗
PubMed1998

Comparison of goserelin and leuprolide in combined androgen blockade therapy.

OBJECTIVES: To perform exploratory analyses of data from a controlled trial that assessed the efficacy and tolerability of two antiandrogens, bicalutamide and flutamide, each combined with monthly depot preparations of leuprolide or goserelin, in patients with Stage D2 prostate cancer. One analysis compared goserelin plus antiandrogen therapy with leuprolide plus antiandrogen therapy; a second analysis compared the four combined androgen blockade (CAB) regimens. METHODS: This was a randomized, multicenter trial, open-label for luteinizing hormone releasing hormone analogue (LHRH-A) therapy, double-blind for antiandrogen therapy, with a two-by-two factorial design. Eight-hundred thirteen patients were allocated in a ratio of 2:1 to goserelin therapy (3.6 mg every 28 days) or leuprolide therapy (7.5 mg every 28 days) and 1:1 to bicalutamide therapy (50 mg once a day) or flutamide therapy (250 mg three times a day). The end points of time to progression and survival were assessed with a median of 160 weeks of follow-up. RESULTS: The percentages of progression events (70.9% versus 73.3%) and deaths (54.3% versus 56.8%) were similar for goserelin plus antiandrogen and leuprolide plus antiandrogen therapies. The hazard ratios for goserelin plus antiandrogen therapy to leuprolide plus antiandrogen therapy were 0.99 (95% confidence interval [CI] 0.84 to 1.18; P = 0.92) and 0.91 (95% CI 0.75 to 1.11; P = 0.34) for time to progression and survival, respectively. Goserelin plus antiandrogen and leuprolide plus antiandrogen therapies were generally well tolerated, and the side effects associated with depot administration occurred with a low frequency in the two groups. There were no significant differences among the goserelin plus bicalutamide, goserelin plus flutamide, or leuprolide plus bicalutamide therapy groups, but leuprolide plus flutamide therapy had a significantly poorer outcome than the other three therapies. The side-effect profiles for the four CAB groups were generally similar; diarrhea was more common among patients treated with flutamide and hematuria was more common among patients treated with bicalutamide. CONCLUSIONS: Although the results of these exploratory analyses should be interpreted with caution, they indicate that goserelin plus antiandrogen and leuprolide plus antiandrogen therapies are similarly well tolerated and have equivalent time to progression and survival, and that leuprolide plus flutamide therapy appears to be the least effective of the four CAB regimens.

Adult↗
PubMed1998

Decreased survival of black Americans with testicular cancer.

PURPOSE: A 14-year review of 215 consecutive patients with testicular cancer at the University of Illinois hospitals revealed that 25% were black. This large experience with this relatively rare cancer in black men provides a unique opportunity to compare the disease stage at presentation, histological tumor type and 5-year survival rates of black, white and Hispanic men. MATERIALS AND METHODS: We reviewed the records of patients with a diagnosis of testicular cancer treated at University of Illinois hospitals. The Kaplan-Meier method was used to calculate actuarial 5-year survival rates. RESULTS: The overall percentages of white, black and Hispanic men were 55 (119 men), 25 (53) and 18% (38), respectively. We found no significant differences in tumor types among the 3 racial groups. Overall 42 and 58% of the patients had seminoma and nonseminoma, respectively. Black men with some types of cancer have been shown to present with higher stages of disease but we noted no differences in clinical stage at presentation in all groups with testicular cancer (average stage I disease in 45%, II in 31% and III in 24%). Survival rates were 88% in white, 79% in Hispanic and 71% in black patients. CONCLUSIONS: Black men had significantly decreased (z <0.02) 5-year disease specific survival, which was 17% less than white patients. The difference in disease specific survival for Hispanic men was not statistically significant. This review of 215 patients with testicular cancer revealed no differences in tumor type or stage at presentation for white, black or Hispanic men. However, a review of these data suggests that disease specific survival outcomes are more ominous in black men.

Actuarial Analysis↗
PubMed1998

Quality of life in metastatic prostate cancer among men of lower socioeconomic status: feasibility and criterion related validity of 3 measures.

PURPOSE: Identification of metastatic disease progression is often difficult but important. Previous studies of quality of life in metastatic disease have been limited by the small number of respondents who were not white or of lower socioeconomic status. Quality of life assessment is generally done using self-administration techniques but this method is of limited usefulness for patients of low socioeconomic status, many of whom have limited reading abilities. We evaluated the feasibility and validity of interviewer administration of 3 quality of life instruments for patients of low socioeconomic status with metastatic prostate cancer. MATERIALS AND METHODS: We used instruments previously validated with self-administration methodology, including the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-30, Functional Assessment of Cancer Therapy-General Scale and Quality of Life Index. Subjects were men with metastatic prostate cancer with stable (78) or progressive (32) disease at 4 Veterans Affairs medical centers and 1 other site. Of the patients 94% were Veterans Affairs patients and more than 60% were black. RESULTS: Each quality of life instrument required less than 10 minutes of interviewer administration and was able to discriminate between patients with stable versus progressive disease on several health status domains. CONCLUSIONS: These data support the feasibility and validity of quality of life measurement in patients of low socioeconomic status with metastatic prostate cancer. Consideration should be given to adding quality of life instruments to patient encounter even among low socioeconomic status, low literacy populations.

Aged↗
PubMed1997

Therapeutic effects of leuprorelin microspheres in prostate cancer.

Leuprorelin has demonstrated effectiveness comparable to orchiectomy and oral diethylstilboestrol for the palliation of advanced prostate cancer. Unlike orchiectomy, leuprorelin's effects are reversible; also leuprorelin is not associated with the cardiovascular or thromboembolic adverse effects of oestrogens. For these reasons, leuprorelin has been widely used as an alternative to surgical castration or to oestrogens in the treatment of metastatic prostate cancer. Sustained-release leuprorelin microsphere formulations have been developed which exhibit zero order release of active drug from the injection site, such that in the United States the 7.5 mg dosage strength is recommended to be administered once a month and the 22.5 mg dosage strength once every three months. Although most patients will have suppressed release of pituitary luteinizing hormone by the third or fourth week after the first dose of depot leuprorelin, 4-5% of treated patients have been reported to have delayed responses, taking many more weeks or months to respond. A transient biochemical hormone escape has also been reported, although worsening of clinical symptoms has not accompanied the elevation of serum testosterone levels during treatment. Usually, leuprorelin is initiated as monotherapy when patients with advanced prostate cancer become symptomatic. However, newer studies of combination therapy of luteinizing hormone releasing hormone analogs with antiandrogens suggest that early initiation of therapy, at the time of diagnosis of advanced disease, may be beneficial, particularly in a subgroup of patients with small volume disease and good performance status. Leuprorelin is also undergoing evaluation as neoadjuvant therapy prior to radical prostatectomy for localized prostate cancer. Preliminary studies suggest that neoadjuvant leuprorelin in combination with an antiandrogen may be effective in downstaging prostate tumours. Leuprorelin commonly produces several adverse effects: hot flashes, decreased libido and impotence, and tumour flare.

Journal Article↗
PubMed1997

Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Casodex Combination Study Group.

OBJECTIVES: To compare the efficacy and tolerability of bicalutamide and flutamide, each combined with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy, in patients with metastatic (Stage D2) prostate cancer. METHODS: This was a randomized, double-blind (for antiandrogen therapy), multicenter study with a two-by-two 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: The median times to progression and death were 97 and 180 weeks for the bicalutamide plus LHRH-A group compared with 77 and 148 weeks for the flutamide plus LHRH-A group. The hazard ratio for time to progression for bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.93 (95% confidence interval [CI] 0.79 to 1.10, P = 0.41) and that for survival time was 0.87 (95% CI 0.72 to 1.05, P = 0.15). The therapies were generally well tolerated. The most common adverse event in the two groups was hot flashes. The incidence of hematuria was significantly higher for the bicalutamide plus LHRH-A group than for the flutamide plus LHRH-A group (12% versus 6%, P = 0.007), but no patient withdrew from therapy because of hematuria. There was a significantly (26% versus 12%, P < 0.001) higher incidence of diarrhea and more withdrawals for diarrhea (25 patients versus 2) for the flutamide plus LHRH-A group relative to the bicalutamide plus LHRH-A group. CONCLUSIONS: With a median follow-up time of 160 weeks, the combination of bicalutamide plus LHRH-A was well tolerated and had equivalent time to progression and survival compared with flutamide plus LHRH-A. Treatment with bicalutamide plus LHRH-A resulted in longer median survival than treatment with flutamide plus LHRH-A.

Adult↗
PubMed1997

Benign prostatic hyperplasia: diagnosis and treatment guideline.

OBJECTIVE: To critique the US Department of Health and Human Services Public Health Service, Agency for Health Care Policy and Research, Clinical Practice Guideline on Benign Prostatic Hyperplasia: Diagnosis and Treatment; and to provide an update on management and treatment of benign prostatic hyperplasia (BPH) since the Guideline was published. DATA SOURCES: A review of the published medical literature in MEDLINE from 1994 to April 1996, limited in focus to drug treatment of BPH, English language, and human subjects, was performed. STUDY SELECTION: Controlled clinical studies of drug treatment for symptomatic BPH that used objective parameters (e.g., urinary flow rate, prostatic volume, voiding symptom scores) were evaluated. A single reviewer assessed each study. DATA EXTRACTION: Study methods, inclusion and exclusion criteria, and treatment outcomes were assessed for all studies. Independent extraction was performed by a single observer. DATA SYNTHESIS: Management of BPH is directed at ameliorating voiding symptoms. For moderate or severe BPH, medical or surgical therapy should be offered to the majority of patients. Medical therapy options include alpha-adrenergic antagonists and finasteride. The former offer the advantage of a more prompt onset of action (within weeks) when compared with finasteride. Finasteride produces a lower response rate and smaller improvement in voiding symptoms. Combination therapy of terazosin and finasteride has not been proven to be more effective than terazosin monotherapy. CONCLUSIONS: When medical therapy is indicated for moderate or severe BPH, alpha-adrenergic antagonists exhibit a faster onset of action and produce greater improvement of voiding symptoms than does finasteride.

Humans↗
PubMed1997

Spontaneous expulsion of an intravesical bullet.

Gunshot wounds of the pelvis are not uncommon. Penetrating injuries of the bladder are usually documented by means of a cystogram. The patient reported here was shot with a small caliber bullet. No extravasation was demonstrated. The authors caution that not all penetrating injuries to the bladder will demonstrate extravasation on a properly performed cystogram.

Adult↗
PubMed1997

A comparison of perspectives on prostate cancer: analysis of utility assessments of patients and physicians.

BACKGROUND: Quality-of-life considerations are important in metastatic prostate cancer. In this study, we interviewed physicians and patients about their assessments and expectations on quality of life as metastatic prostate cancer progresses. METHODS: Physicians and patients made utility assessments of three hypothetical health states for metastatic disease using the time trade-off technique. Scores were bounded on a scale from 0.0 (death) to 1.0 (perfect health). RESULTS: Patients rated each of the health states as less desirable than the physicians. CONCLUSIONS: Physicians and patients differ in their perspectives on expected quality of life with metastatic prostate cancer. Our results emphasize the need to assess patients' utilities directly.

Decision Making↗
PubMed1996

A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate carcinoma. Analysis of time to progression. CASODEX Combination Study Group.

BACKGROUND: A randomized, multicenter trial, double-blind for antiandrogen therapy, compared the antiandrogens bicalutamide and flutamide, each combined with luteinizing hormone-releasing hormone analogue therapy (LHRH-A) in 813 patients with Stage D2 prostate carcinoma. An analysis of time to progression (median follow-up, 95 weeks) was performed to augment previous analyses of time to treatment failure and time to death. METHODS: Patients were randomly assigned 1:1 to double-blind antiandrogen therapy, receiving either bicalutamide (50 mg once daily) or flutamide (250 mg three times daily), and were assigned 2:1 to LHRH-A with goserelin acetate (3.6 mg every 28 days) or leuprolide acetate (7.5 mg every 28 days). The primary endpoint of the trial was time to treatment failure, defined as an adverse event leading to withdrawal of randomized therapy, objective progression, death, or withdrawal from study therapy for any reason. Secondary endpoints were time to death, quality of life, and subjective response. The current analysis of time to progression included progression data collected prospectively for 561 patients (69%) and retrospectively for 252 patients (31%). RESULTS: Disease progression occurred for 223 of 404 patients (55%) in the bicalutamide plus LHRH-A group and for 235 of 409 patients (58%) in the flutamide plus LHRH-A group. The hazard ratio for time to progression of bicalutamide plus LHRH-A to that of flutamide plus LHRH-A was 0.9 (two-sided 95% confidence interval [CI], 0.75 to 1.08; P = 0.26). The upper one-sided 95% CI was 1.05, which met the definition of equivalence (< 1.25). CONCLUSIONS: At a median follow-up time of 95 weeks, bicalutamide plus LHRH-A and flutamide plus LHRH-A had equivalent time to progression.

Adenocarcinoma↗
PubMed1996

Treatment of urinary tract infections: selecting an appropriate broad-spectrum antibiotic for nosocomial infections.

Clinical and in vitro data indicate that cefepime, a fourth-generation cephalosporin, may be a valuable addition in the treatment of serious infections. In this study, hospitalized patients with complicated and uncomplicated urinary tract infection (UTI), for which parenteral therapy was appropriate, were enrolled in a 2:1 ratio open, randomized trial comparing the efficacy and safety of cefepime and ceftazidime. A total of 180 patients, including 6 with concurrent bacteremia, were evaluated for their response to cefepime (n = 118) or ceftazidime (n = 62), both of which were administered by intravenous infusion or intramuscular injection in doses of 500 mg every 12 hours. In cases of complicated UTI, cefepime produced a satisfactory clinical response in 83 of 93 (89%) patients and eradicated 83 of 98 (85%) pathogens. A satisfactory clinical response to ceftazidime was experienced by 43 of 50 (86%) patients; and in 39 of 50 (78%) cases pathogens were eradicated. In uncomplicated cases, the clinical response and bacterial eradication rates for cefepime were 23 of 25 (92%) and 22 of 26 (85%), respectively, and for ceftazidime 12 of 12 (100%) and 11 of 12 (92%). Of the 6 patients with concomitant bacteremia, 5 received cefepime and 1, ceftazidime. The infecting organisms, Escherichia coli and Proteus mirabilis, were eradicated in all cases, although one cefepime-treated patient had an unsatisfactory clinical response. The most common adverse events in both groups were headache, diarrhea, and vomiting; most events were unrelated to therapy. Adverse events forced only a 2% withdrawal of patients in either group. There was local tolerance to both agents, and abnormalities in laboratory values were judged to be clinically insignificant. The results of this study indicate that cefepime can be used safely and successfully to treat both complicated and uncomplicated nosocomial infection of the urinary tract, including cases associated with concurrent bacteremia. Moreover, its safety profile appears comparable to those of other cephalosporins, and local tolerance is similar to that of ceftazidime. No patient in either group required discontinuation of therapy because of local intolerance at the infusion or injection site.

Bacteremia↗
PubMed1996

Enhanced expression of parathyroid hormone-related protein in prostate cancer as compared with benign prostatic hyperplasia.

Parathyroid hormone-related protein (PTHrP) has been shown to be the primary factor responsible for humoral hypercalcemia of malignancy. Recently PTHrP has been shown to be an early-response gene that may be involved in cellular proliferation or differentiation. In addition, PTHrP has been implicated in the pathogenesis of bone metastases. Bone metastases are a significant complication in patients with prostate cancer. We compared the expression of PTHrP by immunohistochemical staining using a monoclonal antibody directed against epitope between amino acids [53-64] in benign prostatic hyperplasia (BPH) with that in various stages of prostate cancer. Tissue sections were obtained on formalin-fixed paraffin-embedded blocks from BPH, well-differentiated prostate cancer, poorly differentiated prostate cancer, lymph node metastases (n = 15 each), and normal prostate (n = 2). In the normal prostate tissue there was no staining observed. In BPH, 13 of 15 tissue samples were positive for PTHrP immunoreactivity. An average of 33% of the cells stained positive with 1+ intensity. All samples from prostate cancer stained positive for PTHrP. In the samples from well-differentiated prostate cancer, an average of 87% of cells stained positive for PTHrP, whereas 100% of cells were positive in poorly differentiated and metastatic tumors. The intensity of staining was 3+ in well-differentiated tumors and 4+ in poorly differentiated tumors. Therefore, the expression of PTHrP is enhanced in prostate cancer as compared with BPH and is greater in poorly differentiated carcinoma as compared with the well-differentiated tumors. The role of PTHrP in the pathogenesis of prostate cancer deserves further study.

Adult↗
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↗