Lifestyle intervention in men with advanced prostate cancer receiving androgen suppression therapy: a feasibility study. Randomized, multicenter, phase II trial of two multicomponent regimens in androgen-independent prostate cancer. Randomized trial of combination chemotherapy in hormone-resistant metastatic prostate carcinoma. The effect of dyadic intervention on self-efficacy, social support, and depression for men with prostate cancer. Improving the quality of life of patients with prostate carcinoma: a randomized trial testing the efficacy of a nurse-driven intervention. Randomized phase II trial of docetaxel plus thalidomide in androgen-independent prostate cancer. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Intermittent versus continuous total androgen blockade in the treatment of patients with advanced hormone-naive prostate cancer: results of a prospective randomized multicenter trial. The continued evaluation of the effects of chemotherapy in patients with advanced carcinoma of the prostate.
Healthy lifestyle behaviors could have a role in ameliorating some of the adverse effects of androgen suppression therapy (AST) in men with prostate cancer. The primary aim of this study was to assess the feasibility of a tapered supervised exercise program in combination with dietary advice in men with advanced prostate cancer receiving AST.
                Advanced prostate cancer patients receiving AST for a minimum of 6 months were randomized to a 12-week lifestyle program comprising aerobic and resistance exercise, plus dietary advice (n = 25), or standard care (n = 25). Exercise behavior, dietary macronutrient intake, quality of life, fatigue, functional fitness, and biomarkers associated with disease progression were assessed at baseline, after the intervention, and at 6 months.
                The lifestyle group showed improvements in exercise behavior (P < 0.001), dietary fat intake (P = 0.001), total energy intake (P = 0.005), fatigue (P = 0.002), aerobic exercise tolerance (P < 0.001), and muscle strength (P = 0.033) compared with standard care controls. Although a high rate of attrition (44%) was observed at 6 months, the improvements in key health outcomes were sustained. No effects on clinical prostate cancer disease markers were observed.
                This preliminary evidence suggests that pragmatic lifestyle interventions have potential to evoke improvements in exercise and dietary behavior, in addition to other important health outcomes in men with advanced prostate cancer receiving AST.
                This study shows for the first time that pragmatic lifestyle interventions are feasible and could have a positive impact on health behaviors and other key outcomes in men with advanced prostate cancer receiving AST. Several multicomponent regimens have been reported to be useful in advanced androgen-independent prostate cancer. We used a randomized phase II design to evaluate and compare two such regimens. Patients were accrued primarily in the community setting.
                Patients with progressive, androgen-independent prostate cancer were randomly assigned to one of two treatments: either ketoconazole/doxorubicin alternating with vinblastine/estramustine (KA/VE) or paclitaxel, estramustine, and oral etoposide (TEE). Patients were prospectively stratified on the basis of disease volume. The primary end points were response and overall survival time.
                A total of 75 patients were registered; 71 are included in the analysis. By the criterion of an 80% prostate-specific antigen reduction maintained for at least 8 weeks, 11 (30%) of 37 patients in the TEE arm responded, whereas 11 (32%) of 34 assigned to KA/VE responded. Median survival was 16.9 months (95% confidence interval [CI], 10.5 to 21.2 months) in the TEE arm and 23.4 months (95% CI, 12.9 to 30.6 months) for patients treated with KA/VE. Many patients (24%) failed to complete at least 6 weeks of therapy, including five (8%) treatment-related early deaths.
                Each of these regimens produced clinically significant responses, and the observed median survival (18.9 months for all 71 patients) compares favorably with previously published results, especially in the community setting. Nonetheless, it is apparent that these first-generation regimens must be applied judiciously, and thus we view efforts at better patient selection and the development of more tolerable therapies as higher priorities than carrying either of these regimens to phase III evaluation in the cooperative group setting. A prospective randomized study was conducted in 51 patients with stage D hormone-resistant prostatic carcinoma, comparing a combination of doxorubicin and lomustine (DC) with cyclophosphamide and 5-FU (CF). Patients were assessed objectively (employing National Prostate Cancer Project criteria) and subjectively (using a numerical scoring scheme). Each regimen was well tolerated with acceptable levels of myelosuppression. The objective partial response rate was 57% for DC and 8% for CF. Objective stabilization occurred, respectively, in 14% and 44% of the patients. Similarly, DC demonstrated a significantly superior subjective response rate (partial plus complete) of 82%, compared to 48% for CF. Patients with poor initial performance status or liver involvement had significantly lower response rates and reduced survival. Overall, there was no significant difference in survival between the two arms, reflecting the similarity between DC and CF in total objective response rate (partial response plus stable disease). DC provided superior palliation and was well tolerated by an essentially geriatric population. Urinary and sexual dysfunctions are side effects of radical prostatectomy (RP) for prostate cancer (PC) that contribute to depression. Despite the effectiveness of support groups at reducing depression in cancer patients, men typically do not participate in them. The purpose of this pilot study was to test the effects of a dyadic intervention (one-to-one support) on social support (Modified Inventory of Socially Supportive Behaviors), self-efficacy (Stanford Inventory of Cancer Patient Adjustment), and depression (Geriatric Depression Scale). Subjects were randomized to group. Controls (N=15; Mage=59.7) received usual care. Experimentals were paired with long-term survivors (LTS) who had RP and who had treatment side effects in common. Experimentals (N=15; Mage=57.5) met with a LTS 8 times in 8 weeks to discuss concerns associated with survivorship. No significant differences were detected on social support, but after 4 weeks, significant differences were present on depression between controls and experimentals, however these differences were not seen at 8 weeks. After 8 weeks, there were also significant differences on self-efficacy between controls and experimentals. Weekly anecdotal data supported the feasibility and acceptance of the intervention that was a low cost strategy effective at reducing depression and increasing self-efficacy in men treated by RP. Future research directions and clinical application is presented.
                Copyright 2003 John Wiley & Sons, Ltd. Treatments for clinically localized prostate carcinoma are accompanied by sexual, urinary, and bowel dysfunction and other sequelae that can result in significant distress and reduced well being. Methods capable of improving quality of life are needed that can be integrated into clinical practice. To address this need, a nurse-driven, cancer care intervention was developed and tested.
                Within 6 weeks after completing treatment, 99 patients, along with their partners, were enrolled into a prospective, controlled trial and were randomized to receive the cancer care intervention or to receive standard care. Participants in the intervention arm met once each month for 6 months with an oncology nurse intervenor, who helped patients identify their quality-of-life needs using an interactive computer program. The intervener then provided education and support tailored to participants' needs. Primary outcome variables included 1) disease-specific quality of life, including sexual, urinary, and bowel outcomes and cancer worry; 2) depression; 3) dyadic adjustment; and 4) general quality of life. Outcomes data were collected prior to randomization and again at 4 months, 7 months, and 12 months posttreatment.
                Patients in the intervention arm experienced long-term improvements in quality-of-life outcomes related to sexual functioning and cancer worry compared with patients who received standard care. Baseline depression moderated the impact of the intervention on several other quality-of-life outcomes.
                The findings of the current study indicated that a computer-assisted, nurse-driven intervention was capable of providing durable improvements in the quality of life of men who underwent treatment for clinically localized prostate carcinoma. Both docetaxel and thalidomide have demonstrated activity in androgen-independent prostate cancer (AIPC). We compared the efficacy of docetaxel to docetaxel plus thalidomide in patients with AIPC.
                Seventy-five patients with chemotherapy-naïve metastatic AIPC were randomly assigned to receive either docetaxel 30 mg/m(2) intravenously every week for 3 consecutive weeks, followed by a 1-week rest period (n = 25); or docetaxel at the same dose and schedule, plus thalidomide 200 mg orally each day (n = 50). Prostate-specific antigen (PSA) consensus criteria and radiographic scans were used to determine the proportion of patients with a PSA decline, and time to progression.
                After a median potential follow-up time of 26.4 months, the proportion of patients with a greater than 50% decline in PSA was higher in the docetaxel/thalidomide group (53% in the combined group, 37% in docetaxel-alone arm). The median progression-free survival in the docetaxel group was 3.7 months and 5.9 months in the combined group (P =.32). At 18 months, overall survival in the docetaxel group was 42.9% and 68.2% in the combined group. Toxicities in both groups were manageable after administration of prophylactic low-molecular-weight heparin in the combination group.
                In this randomized phase II trial, the addition of thalidomide to docetaxel resulted in an encouraging PSA decline rate and overall median survival rate in patients with metastatic AIPC. After the prophylactic low-molecular-weight heparin was instituted to prevent venous thromboses, the combination regimen was well tolerated. Larger randomized trials are warranted to assess the impact of this combination. To study the efficacy and safety of dutasteride, a dual inhibitor of the 5-alpha-reductase isoenzymes types I and II.
                A total of 4325 men (2951 completed) with clinical benign prostatic hyperplasia, moderate to severe symptoms (American Urological Association-Symptom Index score of 12 points or greater), a peak flow rate of 15 mL/s or less, a prostate volume of 30 cm3 or greater (as measured by transrectal ultrasonography), and a serum prostate-specific antigen level of 1.5 to 10.0 ng/mL (inclusive) were enrolled into three identical clinical trials and randomized to 0.5 mg dutasteride daily or placebo. After a 1-month, single-blind, placebo lead-in, patients were followed up for 24 months in a double-blind trial with multiple interval assessments.
                At 24 months, serum dihydrotestosterone was reduced from baseline by a mean of 90.2% (median -93.7%; P <0.001), and the total prostate and transition zone volumes were reduced by a mean of 25.7% and 20.4%, respectively (P <0.001). The symptom score was improved by as early as 3 months, with pooled significance from 6 months onward (P <0.001) and a reduction of 4.5 points (21.4%) at 24 months (P <0.001). The maximal flow rate improved significantly from 1 month (P <0.01), with an increase of 2.2 mL/s reported at 24 months (P <0.001). Hence, the risk reduction of acute urinary retention was 57% and the risk reduction of benign prostatic hyperplasia-related surgical intervention was 48% compared with placebo. The drug was well tolerated.
                Dutasteride is a potent inhibitor of dihydrotestosterone production that is safe and effective in terms of the reduction of prostate volume and symptoms, flow rate improvement, and the reduction of the risk of acute urinary retention and surgery during a 24-month study period. The aim of this study was to compare the efficacy of total intermittent androgen deprivation (IAD) versus total continuous androgen deprivation (CAD) for treating patients with advanced prostate cancer in a phase III randomized trial. A total of 68 evaluable patients with hormone-naive advanced or relapsing prostate cancer were randomized to receive combined androgen blockade according to a continuous (n = 33) or intermittent (n = 35) regimen. Therapeutic monitoring was assessed by use of serum prostate-specific antigen (PSA) measurements. Patients in the CAD and IAD groups were equally stratified for age, biopsy Gleason score, and baseline serum PSA levels. The outcome variable was time to androgen-independence of the tumor, which was defined as increasing serum PSA levels despite androgen blockade. Mean follow-up was 30.8 months. The 35 IAD-treated patients completed 91 cycles, and 19 of them (54.3%) completed > or = 3 cycles. Median cycle length and percentage of time off therapy were 9.0 months and 59.5, respectively. The estimated 3-year progression rate was significantly lower in the IAD group (7.0% +/- 4.8%) than in the CAD group (38.9% +/- 11.2%, P = 0.0052). Our data suggest that IAD treatment may maintain the androgen-dependent state of advanced human prostate cancer, as assessed by PSA measurements, at least as long as CAD treatment. Further studies with longer follow-up times and larger patient cohorts are needed to determine the comparative impacts of CAD and IAD on survival. The response and duration of survival were evaluated for patients with stage D relapsing prostatic cancer who were randomized to cyclophosphamide (cytoxan), 5-fluorouracil (5-FU) or standard therapy, or to subsequent chemotherapies. The chemotherapies on initial randomization were superior to the standard therapy in the number of responders and duration of response. Survival was longer for responders (stable or partial regression) on chemotherapy by comparison to responders (stable only) on standard therapy. The survival for patients receiving initial and crossover chemotherapy was significantly improved for patients who responded to therapy. Chemotherapy of advanced relapsing stage D prostatic cancer is more beneficially treated by specific chemotherapy as shown in this randomized study.
PDE5 inhibitors are an effective treatment for SD secondary to treatments for prostate cancer. Other interventions identified need to be tested in further RCTs. The SD interventions in this review are not representative of the range available for men and women. Further evaluations are needed for these interventions for SD following cancer treatments.