Treatment of androgen‐independent prostate cancer with dexamethasone: A prospective study in stage D2 patients

Sakaguchi, Takashi; Tsushima, Tomoyasu; Yamato, Toyoko; Ohashi, Takuma; Suyama, Bunzo; Arata, Ryoji; Nasu, Yasutomo; Kumon, Hiromi

doi:10.1046/j.1442-2042.2001.00302.x

Cited by 37 publications

(25 citation statements)

References 13 publications

(30 reference statements)

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“…Both prednisone (101) and dexamethasone (102,103) have shown some antitumor activity in patients with AIPC, but the mechanisms responsible for their effects are not fully known. Dexamethasone treatment, however, is known to affect IB␣ and IL-6 regulation in multiple myeloma, a cancer that is highly sensitive to bortezomib (104), and both these mechanisms may be important in prostate cancer (48).…”

Section: Introductionmentioning

confidence: 99%

Bortezomib as a Potential Treatment for Prostate Cancer

2004

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Androgen ablation and chemotherapy provide effective palliation for most patients with advanced prostate cancer, but eventually progressing androgen-independent prostate cancer threatens the lives of patients usually within a few years, mandating improvement in therapy. Proteasome inhibition has been proposed as a therapy target for the treatment of solid and hematological malignancies. The proteasome is a ubiquitous enzyme complex that is a hub for the regulation of many intracellular regulatory pathways; because of its essential function, this enzyme has become a new target for cancer treatment. Studies with bortezomib (VELCADE, formerly known as PS-341) and other proteasome inhibitors indicate that cancer cells are especially dependent on the proteasome for survival, and several mechanisms used by prostate cancer cells require proteasome function. Bortezomib has been studied extensively in vitro and in vivo, and anticancer activity has been seen in cell and animal models for several solid tumor types, including prostate cancer. A Phase I trial to determine the maximum tolerated dose of once-weekly bortezomib has been completed. This trial included a large fraction of patients with androgenindependent prostate cancer. The maximum tolerated dose was reached at 1.6 mg/m 2 . A correlation was seen among bortezomib dose, proteasome inhibition, and positive modulation of serum prostate-specific antigen. There was also evidence of down-regulation of serum interleukin 6, a downstream nuclear factor B effector. This Phase I trial and preclinical studies support additional testing of bortezomib in combination with radiation or chemotherapy for androgen-independent prostate cancer.

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Section: Introductionmentioning

confidence: 99%

Bortezomib as a Potential Treatment for Prostate Cancer

2004

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“…Reported effects are linked to decreased prostate specific antigen levels and amelioration of symptoms 12 .…”

Section: Discussionmentioning

confidence: 99%

Deleterious effects of prepubertal corticosterone treatment on rat prostate

Pinto

Silva

et al. 2015

Acta Cir. Bras.

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PURPOSE:To investigate the structural and functional changes induced by corticosterone (CORT) in the ventral prostrate (VP) of rats in order to study chronic stress effects in the prepubertal phase. METHODS:Wistar rats received daily saline or CORT injections during the pubertal period from the 5th to 25th day of postnatal life.The animals were distributed into four groups: 1 -Control (n=5); 2 -Control 99mTc-P (n=5); 3 -Treated with CORT (n=14); 4 -Treated with CORT and 99mTc-P (n=10). All rats were sacrificed at two months of age. Technical tissue uptakes of 99mTc-P were used to evaluate the functional and stereological methods for morphological analysis. RESULTS:Acini distribution in the group treated with CORT differed significantly (p<0.0001) from the control. The control group's epithelial average height (10.01±0.24 microns) was statistically significant (p<0.0001) from rats treated with CORT (19.27±0.73microns).The collagen distribution was lower in the treated group (2.79%) when compared to control (3.97%). The radioactivity percentage in the groups marked with 99mTc-P (%Ati/g) did not demonstrate a statistically significant difference (p=0.285897). CONCLUSION:Chronic administration of corticosterone in prepubertal rats causes changes in their acinar structure and their ventral prostate stroma, indicating possible deleterious effects of this hormone.

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“…A PSA response, with a reduction >50%, was seen in 5 of those patients (27.8%). 45 Another retrospective study from the Mayo Clinic reported a PSA reduction >50% in 23 of 38 patients (61%) who were treated with dexamethasone. 43 The combination of dexamethasone with calcitriol may provide additive benefit, based on data from preclinical models.…”

Section: Discussionmentioning

confidence: 99%

“…Other investigators have reported the positive clinical effects of dexamethasone in patients with prostate cancer. [43][44][45] In 1 study, 19 patients with HRPC were treated prospectively with 1.5 mg of dexamethasone daily. A PSA response, with a reduction >50%, was seen in 5 of those patients (27.8%).…”

Section: Discussionmentioning

confidence: 99%

A phase II trial of dexamethasone, vitamin D, and carboplatin in patients with hormone‐refractory prostate cancer

Flaig

Barqawi

Miller

et al. 2006

Cancer

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BACKGROUND.A Phase II prospective trial was performed to study the efficacy of combination therapy with dexamethasone, calcitriol (1,25‐dihydroxyvitamin D3), and carboplatin in patients with hormone‐refractory prostate cancer (HRPC). Preclinical data from prostate cancer cell lines suggested a synergistic effect of these therapies.METHODS.All patients had pathologically confirmed prostate cancer with at least 2 consecutive increases in prostate‐specific antigen (PSA). Treatment started with 1 mg of oral dexamethasone given daily with 0.5 mcg of daily calcitriol added at the start of Week 5. Carboplatin (area under the concentration time curve = 2) was started at the beginning of Week 7. Initially, carboplatin was given weekly; however, the protocol was changed later to give carboplatin for the first 4 weeks of a 6‐week cycle. Of 40 patients who consented to participate, 6 patients were ineligible or declined to start therapy, leaving 34 treated patients. The median follow‐up was 80.7 weeks (range, 11.5–260 weeks).RESULTS.A formal PSA response was seen in 13 of 34 treated patients (38.2%; 95% confidence interval [95% CI], 22.2–56.4%). The median overall survival was 97.7 weeks (95% CI, 61–114 weeks). Significant adverse events that were observed during the trial period included 2 deaths (myocardial infarction and cardiogenic shock), 4 patients with Grade 3 neutropenia (according to the National Cancer Institute Common Toxicity Criteria, version 2.0), 2 patients with thrombosis, 2 patients with inflammatory bowel symptoms, and 2 patients with new‐onset diabetes mellitus.CONCLUSIONS.The novel combination of dexamethasone, calcitriol, and carboplatin for patients with HRPC produced a PSA response in 13 of 34 patients and had an acceptable side‐effect profile. Cancer 2006. © 2006 American Cancer Society.

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Treatment of androgen‐independent prostate cancer with dexamethasone: A prospective study in stage D2 patients

Cited by 37 publications

References 13 publications

Bortezomib as a Potential Treatment for Prostate Cancer

Bortezomib as a Potential Treatment for Prostate Cancer

Deleterious effects of prepubertal corticosterone treatment on rat prostate

A phase II trial of dexamethasone, vitamin D, and carboplatin in patients with hormone‐refractory prostate cancer

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