Systematic review and meta‐analysis of monotherapy compared with combined androgen blockade for patients with advanced prostate carcinoma

Samson, Jim; Seidenfeld, Jerome; Schmitt, Brian P.; Hasselblad, Vic; Albertsen, Peter C.; Bennett, Charles L.; Wilt, M.; Aronson, Naomi

doi:10.1002/cncr.10647

Cited by 227 publications

(136 citation statements)

References 48 publications

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“…With a response rate of about 80%, androgen ablation induces apoptosis of normal prostate epithelial cells as well as regression of early-stage prostate cancer. However, progression to androgen independence occurs over time, so that this treatment option is not curative (Samson et al, 2002). Conventional chemotherapy has not sufficiently been proven to be effective either, especially in androgen-independent prostate cancer, and is limited by toxicity that is often aggravated by comorbidity of the elderly prostate cancer patients (Yagoda and Petrylak, 1993).…”

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confidence: 99%

Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer

et al. 2004

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Histone deacetylase inhibitors (HDACs) are known to exhibit antiproliferative effects on various carcinoma cells. In this study, the in vivo efficiency of two HDACs, sodium butyrate and tributyrin, on prostate cancer growth inhibition were investigated. To gain an insight into the possible underlying pathways, cell culture experiments were performed focusing on the expression of p21, Rb and cmyc. For in vivo testing, prostate cancer cell lines (PC3 and TSU-Pr1) were seeded on the chorioallantois membrane (CAM) and implanted in a xenograft model using nude mice. Standard Western blot analysis was performed for protein expression of p21, Rb and c-myc in HDAC-treated vs untreated prostate cancer cells. Both sodium butyrate and tributyrin had a considerable treatment effect on microtumours on the chicken egg at already very low concentrations of 0.1 mM. Tributyrin-treated tumours showed the strongest effect with 38% apoptotic nuclei in the prostate cancer cell line PC3. In the mouse model, there was almost no difference between sodium butyrate and tributyrin. In untreated animals the tumours were almost double the size 4 weeks after implantation. Tumours of the treatment groups had a significantly lower percentage of Ki-67-positive-stained nuclei. As demonstrated by Western blot analysis, these effects seem to be independent of p53 status and a pathway via p21 -Rb -c-myc is possibly involved. In this study we have demonstrated a substantial in vivo treatment effect, which can be induced by the application of sodium butyrate or the orally applicable tributyrin in human prostate cancer. The given results may provide the rationale to apply these drugs in well-controlled clinical trials in patients being at high risk of recurrence after specific therapy or in patients with locally or distant advanced prostate cancer.

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confidence: 99%

Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer

et al. 2004

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“…Still some benefit through surgery and adjuvant hormonal treatment in these advanced cases is reported. 5,11,22 In fact, there is evidence that radical prostatectomy with early adjuvant androgen deprivation provides a significant advantage compared to androgen suppression alone as goes for overall and disease-specific survival. 23 Presently, less advanced cases are diagnosed due to increasing awareness of the population and the merit of PSA as a screening tool.…”

Section: Radiation or Surgery In Advanced Prostate Cancer R Kuefer Et Almentioning

confidence: 99%

Comparison of external radiation therapy vs radical prostatectomy in lymph node positive prostate cancer patients

Kuefer

Volkmer

Loeffler

et al. 2004

Prostate Cancer Prostatic Dis

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Introduction: Treatment options for lymph node positive prostate cancer are limited. We retrospectively compared patients who underwent external radiotherapy (ERT) to patients treated by radical prostatectomy (RPX). Materials and Methods: A total of 102 lymph node positive patients from the RPX series at Ulm University were evaluated. In all, 76 patients received adjuvant androgen withdrawal as part of their primary treatment. In the ERT group, 44 patients were treated at the University of Michigan using a fractionated regimen. Of these, 21 patients received early adjuvant hormonal therapy. Patients with neoadjuvant therapy before RPX or ERT were excluded. Results: In the RPX group, PSA nadir (nadirp0.2 vs 40.2 ng/ml) showed a strong association with outcome. In the ERT group, pretreatment PSA was an independent predictor of outcome (P ¼ 0.04) and patients with adjuvant hormonal therapy had a significant longer recurrence-free interval compared to patients without adjuvant therapy (P ¼ 0.004). Comparing only patients with adjuvant hormonal treatment after cancer-specific therapy, the ERT-treated patients had a borderline longer PSA recurrence-free survival time compared to the RPX-treated patients (P ¼ 0.05). Conclusions: In case of positive lymph nodes, RPX and ERT might be considered and need to be explained to the patient. For future treatment decisions, the presented findings and a potential survival benefit need to be evaluated in a larger prospective setting.

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“…[15][16][17][18][19][20][21][22][23] Using these references, [15][16][17][18][19][20][21][22][23] the composite value for the incidence of side effects due to short-term therapy was estimated to be 0.20. Because precise estimates for individual toxicities are not provided in any particular reference, this value was obtained by doubling the approximate hormone withdrawal rate, as hormones usually were withdrawn when side effects were intolerable.…”

Section: Adjustment For Side Effects and Relative Importance Of Survimentioning

confidence: 99%

“…Prolonging the duration of hormone therapy increases the risk of each of the side effects listed above, particularly fatigue, osteoporosis, gynecomastia, and sexual side effects. [15][16][17][18][19][20][21][22][23] Based on these references, the composite value for the incidence of side effects of long-term hormone therapy was estimated to be 0.60, a value that also was calculated by doubling the approximate withdrawal rate. Although the authors recognize that these incidence values are approximate and somewhat arbitrary, the model that has been developed is far less dependent on the incidence of side effects than on the detriment to quality of life that results from these side effects.…”

Section: Adjustment For Side Effects and Relative Importance Of Survimentioning

confidence: 99%

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Hormone therapy adjuvant to external beam radiotherapy for locally advanced prostate carcinoma

Jani

Kao

Hellman

2003

Cancer

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BACKGROUNDHormone therapy commonly is used to treat metastatic, locally advanced, and localized prostate carcinoma. The objective of the current investigation was to determine, using the number‐needed‐to‐treat (NNT) method, the effect of using hormone therapy to treat locally advanced disease, with consideration given to both the complications and the known advantages associated with hormone therapy.METHODSA literature review was performed to determine 1) the absolute benefit, based on available clinical endpoints, associated with the addition of hormone therapy to external beam radiotherapy for locally advanced prostate carcinoma; 2) the incidence of side effects of short‐term and long‐term hormone therapy; and 3) the stepwise progression from biochemical failure to death. A model was constructed to estimate the complication/utility‐adjusted survival detriment resulting from the side effects of short‐term (≤ 6 months) and long‐term (> 6 months) hormone therapy, and the absolute/unadjusted and complication‐adjusted NNTs for the addition of short‐term and long‐term hormone therapy were computed. In all cases, the magnitudes and signs of the NNTs obtained were used to gauge the effect of hormone therapy.RESULTSThe unadjusted NNTs were positive and in most cases had relatively small magnitudes (the greater the NNT, the smaller the benefit) for both short‐term and long‐term hormone therapy; these results were expected, and they suggested that there is a strong benefit associated with the use of hormones adjuvant to radiotherapy for locally advanced disease. Adjusted NNTs remained positive and had relatively small magnitudes even after the introduction into the analysis of complications of short‐term and long‐term hormone therapy. This finding, although weak with respect to the effect of short‐term hormone therapy on cause‐specific survival, remained robust over the range of values for utility impairment expected from short‐term and long‐term hormone therapy.CONCLUSIONSThe benefits of short‐term and long‐term hormone therapy for locally advanced prostate carcinoma appear to be significant and to outweigh the associated side effects. Long‐term therapy appears to be better than short‐term therapy in terms of virtually all endpoints studied, even when the increased incidence of side effects is considered. The current investigation was successful in the use of the complication‐adjusted NNT method for oncologic and radiotherapeutic scenarios in which the results of randomized trials could be summarized, adjusted for treatment toxicity, and individualized to a given patient. Cancer 2003. © 2003 American Cancer Society.

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Systematic review and meta‐analysis of monotherapy compared with combined androgen blockade for patients with advanced prostate carcinoma

Cited by 227 publications

References 48 publications

Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer

Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer

Comparison of external radiation therapy vs radical prostatectomy in lymph node positive prostate cancer patients

Hormone therapy adjuvant to external beam radiotherapy for locally advanced prostate carcinoma

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